Glp-1 and glucagon dual agonist peptides with improved biological stability

ABSTRACT

GLP-1 and glucagon dual agonists disclosed herein have improved biological stability, including proteolytic stability, and duration of action. The peptides can be administered about once a week.

CROSS REFERENCE TO RELATED APPLICATION

This application claims the benefit of U.S. Provisional Application 63/307,206 filed on Feb. 7, 2022, the content of which is hereby incorporated by reference in its entirety.

REFERENCE TO A SEQUENCE LISTING

This application is accompanied by an XML file as a computer readable form containing the sequence listing entitled, “GLPGGQW-100.xml”, created on Feb. 13, 2023, with a file size of 1,417,216 bytes, the content of which is hereby incorporated by reference in its entirety.

BACKGROUND OF THE INVENTION

The incidence of obesity and diabetes have been rising in epidemic proportions. Diabetes is characterized by high levels of blood glucose resulting from defects in insulin production, insulin action, or both. Type 2 diabetes mellitus (T2DM) accounts for some 90 to 95 percent of all diagnosed cases of diabetes, and the risk of type 2 diabetes rises with increasing body weight. The prevalence of type 2 diabetes is three to seven times higher in those who are affected by obesity than in normal weight adults, and is 20 times more likely in those with a body mass index (BMI) greater than 35 kg/m². However, weight-loss can improve control or cure type 2 diabetes.

Glucagon and glucagon-like peptide-1 (GLP-1) derive from pre-proglucagon, a 158 amino acid precursor polypeptide that is processed in different tissues to form a number of different proglucagon-derived peptides, including glucagon, glucagon-like peptide-1 (GLP-1), glucagon-like peptide-2 (GLP-2) and oxyntomodulin (OXM), that are involved in a wide variety of physiological functions, including glucose homeostasis, insulin secretion, gastric emptying, and intestinal growth, as well as the regulation of food intake. Glucagon is a 29-amino acid peptide that corresponds to amino acids 33 through 61 of proglucagon (53 to 81 of preproglucagon), while GLP-1 is produced as a 37-amino acid peptide that corresponds to amino acids 72 through 108 of proglucagon (92 to 128 of preproglucagon). GLP-1(7-36) amide or GLP-1(7-37) acid are biologically active forms of GLP-1, that demonstrate essentially equivalent activity at the GLP-1 receptor.

Glucagon is produced by the pancreas and interacts with the glucagon receptor (“glucR”). Glucagon acts in the liver to raise blood glucose via gluconeogenesis and glycogenolysis. When blood glucose begins to fall, glucagon signals the liver to break down glycogen and release glucose, causing blood glucose levels to rise toward a normal level.

GLP-1 has different biological activities compared to glucagon. It is secreted from gut L cells and binds to the GLP-1 receptor. Its activities include stimulation of insulin synthesis and secretion, inhibition of glucagon secretion, and inhibition of food intake.

Both glucagon and GLP-1, acting as agonists at their respective receptors, have been shown to be effective in weight loss. Certain GLP-1 analogs are being sold or are in development for treatment of obesity including, e.g., Liraglutide (Saxenda® from Novo Nordisk) and Semaglutide (Wegovy® from Novo Nordisk). Glucagon/GLP-1 dual agonist peptides such as cotadutide are also known and are in clinical development for treatment of diabetes, obesity, and nonalcoholic steatohepatitis (NASH). However, all of these proposed therapies involve chronic self-medication necessitating patient compliance over an extended period of time. Other peptides, e.g., amylin analogues are also being considered for the treatment of obesity, excess food intake, and diabetes (WO 2018/046719).

Accordingly, there remains a need for therapeutics that can agonize both GLP-1 and glucagon functions to e.g., improve glycemic control, reduce weight, treat type 2 diabetes mellitus, (T2DM) and/or treat NASH, while minimizing burdens associated with administration to improve patient compliance and quality of life.

BRIEF SUMMARY OF THE INVENTION

Provided herein are GLP-1 and glucagon dual agonists with improved biological stability (e.g., proteolytic stability) and duration of action. The GLP-1 and glucagon dual agonist peptides provided herein can have improved properties, e.g., as compared to semaglutide H(Aib)EGTFTSDVSSYLEGQAAX20EFIAWLVRGRG-acid, wherein X20=Lys[O2Oc-O2Oc-γE-C18diacid] (SEQ ID NO: 539)) and/or cotadutide (HSQGTFTSDX10SEYLDSERARDFVAWLEAGG-acid, wherein X10=Lys[ε-γE-Palmitoyl] (SEQ ID NO: 538)). Accordingly, the GLP-1 and glucagon dual agonist peptides provided herein can be administered once weekly.

Certain aspects of the disclosure are directed to a peptide comprising the sequence: H-X2-X3-G-X5-X6-T-S-D-X10-S-X12-αMethyl-Phenylalanine (αMePhe)-L-X15-X16-X17-X18-A-X20-X21-X22-X23-X24-X25-X26-X27-X28-X29-X30-X31-Z, wherein X2 is Aminoisobutyric acid (Aib), S, or A, X3 is Q, H, or E, X5 is T or S, X6 is F or αMePhe, X10 is V, K or Y, X12 is K, E, or S, X15 is D or E, X16 is T, S, or G, X17 is K, R, E, or Q, X18 is R or A, X20 is R, K, or Q, X21 is D or E, X22 is αMePhe or F, X23 is V or I, X24 is Q or A, X25 is Aib or W, X26 is L or I, X27 is L, A, E, V, or M, X28 is E, N, A, R, or K, X29 is Aib, T, or G, X30 is G, R, or not present, X31 is G or not present, and Z is amide or acid (SEQ ID NO: 540).

In some aspects, X2 is Aib. In some aspects, X3 is Q. In some aspects, X3 is H. In some aspects, X5 is T. In some aspects, X5 is S. In some aspects, X6 is F. In some aspects, X6 is αMePhe. In some aspects, X10 is V. In some aspects, X12 is K. In some aspects, X15 is D. In some aspects, X16 is T. In some aspects, X16 is S. In some aspects, X17 is K. In some aspects, X17 is R. In some aspects, X18 is R. In some aspects, X18 is A. In some aspects, X20 is R. In some aspects, X20 is K. In some aspects, X21 is D. In some aspects, X22 is F. In some aspects, X22 is αMePhe. In some aspects, X23 is V. In some aspects, X24 is Q. In some aspects, X25 is W. In some aspects, X25 is Aib. In some aspects, X26 is L. In some aspects, X26 is I. In some aspects, X27 is L. In some aspects, X27 is A. In some aspects, X28 is E. In some aspects, X28 is N. In some aspects, X29 is Aib. In some aspects, X29 is T. In some aspects, X30 is G. In some aspects, X30 is not present. In some aspects, X31 is not present. In some aspects, Z is amide. In some aspects, Z is acid.

In some aspects, X2 is Aib, X12 is K, and X24 is Q. In some aspects, X16 is T, X17 is K, X27 is L, X28, is E, and X29 is Aib. In some aspects, X3 is Q, X5 is T, X6 is F, X10 is V, X12 is K, X15 is D, X16 is T, X17 is K, X18 is R, X20 is R, X21 is D, X22 is F, X23 is V, X24 is Q, X25 is W, X26 is L, X27 is L, X28 is E, X29 is Aib, X30 is G, X31 is not present, and Z is acid. In some aspects, X3 is H, X5 is S, X6 is αMePhe, X10 is V, X12 is K, X15 is D, X16 is S, X17 is R, X18 is A, X20 is K, X21 is D, X22 is αMePhe, X23 is V, X24 is Q, X25 is Aib, X26 is I, X27 is A, X28 is N, X29 is T, X30 is not present, X31 is not present, and Z is amide.

In some aspects, one or more lysine residues are acylated. In some aspects, the lysine at position 17 is acylated. In some aspects, the lysine at position 20 is acylated.

In some aspects, one or more lysine resides are lipidated. In some aspects, the lysine at position 17 is lipidated. In some aspects, the lysine at position 20 is lipidated.

In some aspects, the lipid is selected from the group consisting of octadecanedioic acid (C18diacid) and icosanedioic acid (C20diacid). In some aspects, the lipid is octadecanedioic acid (C18diacid). In some aspects, the lipid is icosanedioic acid (C20diacid). In some aspects, the lipid is linked to the epsilon amino group of lysine at position 17 or 20 via a linker.

In some aspects, the linker is ((O2Oc)-(O2Oc)-γE) or ((O2Oc)-(O2Oc)-γE-γE) in the C- to N-terminal orientation. In some aspects, the linker is ((O2Oc)-(O2Oc)-γE) in the C- to N-terminal orientation. In some aspects, the linker is ((O2Oc)-(O2Oc)-γE-γE) in the C- to N-terminal orientation. In some aspects, the linker is linked to the epsilon amino group of the residue at position 17 or 20.

Certain aspects of the disclosure are directed to a peptide comprising the sequence of H-Aib-Q-G-T-F-T-S-D-V-S-K-αMePhe-L-D-T-K-R-A-R-D-F-V-Q-W-L-L-E-Aib-G-acid (SEQ ID NO: 541).

In some aspects, the lysine at position 17 is acylated and lipidated, the lipid is linked to the acylated lysine via its epsilon amino group to ((O2Oc)-(O2Oc)-γE) linker in the C to N terminal orientation, and the lipid is octadecanedioic acid (C18diacid). In some aspects, the lysine at position 17 is acylated and lipidated, the lipid is linked to the acylated lysine via its epsilon amino group to ((O2Oc)-(O2Oc)-γE) linker in the C to N terminal orientation, and the lipid is icosanedioic acid (C20diacid).

Certain aspects of the disclosure are directed to a peptide comprising the sequence H-Aib-H-G-S-αMePhe-T-S-D-V-S-K-αMePhe-L-D-S-R-A-A-K(ε-(O2Oc)-(O2Oc)-γE-C18diacid)20-D-αMePhe-V-Q-Aib-1-A-N-T-amide (SEQ ID NO: 228).

Certain aspects of the disclosure are directed to a peptide comprising the sequence H-Aib-H-G-S-αMePhe-T-S-D-V-S-K-αMePhe-L-D-S-R-A-A-K(ε-(O2Oc)-(O2Oc)-γE-γE-C20diacid)20-D-αMePhe-V-Q-Aib-I-A-N-T-amide (SEQ ID NO: 233).

In some aspects, the peptide binds to the GLP-1 receptor (GLP-1R), binds to the glucagon receptor (GCGR), or binds to both a GLP-1 receptor and a glucagon receptor. In some aspects, the GLP-1R is a human GLP-1R. In some aspects, the GCGR is a human GCGR.

In some aspects, the peptide is an agonist of GLP-1 activity, an agonist of glucagon activity, or an agonist of both GLP-1 and glucagon activity. In some aspects, the peptide has increased proteolytic-resistance relative to the natural ligand of the GLP-1R and/or GCGR.

In some aspects, the peptide is isolated.

In some aspects, the peptide has at least 50%, at least 60%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95, or 100% of intact peptide remaining after incubation with a protease at 37° C. for 5 min, 10 min, 15 min, 30 min, 2 hr, 4 hr, or 24 hr. In some aspects, the protease is selected from the group consisting of neprilysin, pepsin, pancreatin, simulated gastric fluid with pepsin, and simulated intestinal fluid with pancreatin.

In some aspects, the peptide has a half-life in cynomolgus monkeys after intravenous administration of at least 45 hours, at least 50 hours, at least 60 hours, at least 70 hours, at least 80 hours, at least 90 hours, at least 100 hours, at least 110 hours, at least 120 hours, or about 130 hours. In some aspects, the peptide has an s.c. bioavailability in cynomolgus monkeys of at least 75%, at least 80%, at least 90%, or about 95%.

In some aspects, a pharmaceutical composition comprising the peptide is provided herein. In some aspects, the composition is a solid composition. In some aspects, the composition is a liquid composition.

In some aspects, provided herein is a method of treating or preventing a disease or condition caused or characterized by excess body weight, wherein the method comprises administering to a subject in need of treatment an effective amount of any peptide or composition provide herein. In some aspects, the disease or condition is obesity. In some aspects, the disease or condition is type 2 diabetes.

In some aspects, provided herein is a method of treating or preventing non-alcoholic steatohepatitis (NASH), wherein the method comprises administering to a subject in need of treatment an effective amount of any peptide or composition provide herein.

In some aspects of a method provided herein, the administration is by injection. In some aspects of a method provided herein, the administration is oral. In some aspects of a method provided herein, the administration decreases body weight of the subject, increases insulin secretion in the subject, delays gastric emptying in the subject, decreases food intake in the subject, increases mitochondria function in the subject, inhibits de novo lipogenesis in the subject, decreases HbA1c in the subject, enhances fatty oxidation in the subject, decreases hepatic mitochondrial oxidative stress in the subject, decreases steatosis in the subject, decreases fibrosis in the subject, decreases glycogen synthesis in the subject, increases gluconeogenesis in the subject, halts disease progression in the subject, reverses fibrosis in the subject, and/or reduces risk of death due to cirrhosis, hepatocellular carcinoma, and/or cardiorenal disease in the subject. In some aspects of a method provided herein, the subject is a human. In some aspects of a method provided herein, the peptide is administered about once a week.

BRIEF DESCRIPTION OF THE DRAWINGS/FIGURES

FIGS. 1A-1G are drawings depicting the exemplary lipids icosanedioic acid (C20diacid) (FIG. 1A), octadecanedioic acid (C18diacid) (FIG. 1B), stearoyl (FIG. 1C), margaroyl (FIG. 1D), palmitoyl (FIG. 1E), myristoyl (FIG. 1F), and lauryl (FIG. 1G).

FIGS. 2A-2F are drawings depicting exemplary linkers attached to lipids depicted in FIGS. 1A-1G 2-(2-(2-aminoethoxy)ethoxy)acetic acid (O2Oc) (FIG. 2A), (O2Oc)-(O2Oc) (FIG. 2B), (O2Oc)-γE-(O2Oc) (FIG. 2C), (PEG)2-(PEG)2-γE-γE (FIG. 2D), (PEG)2-γE-(PEG)2-γE (FIG. 2E), gammaglutamic acid (γE) (FIG. 2F), γE-(O2Oc) (FIG. 2G), γE-(O2Oc)-(O2Oc) (FIG. 2H), γE-(O2Oc)-γE-(O2Oc) (FIG. 2I), γE-(PEG)2-(PEG)2 (FIG. 2J), γE-(PEG)2-γE-(PEG)2 (FIG. 2K), γE-(PEG)4 (FIG. 2L), γE-γE (FIG. 2M), γE-γE-(O2Oc) (FIG. 2N), γE-γE-(O2Oc)-(O2Oc) (FIG. 2O), γE-γE-(PEG)12 (FIG. 2P), γE-γE-(PEG)2-(PEG)2 (FIG. 2Q), γE-γE-(PEG)2-γE-γE (FIG. 2R), γE-γE-(PEG)4 (FIG. 2S), γE-γE-(PEG)8 (FIG. 2T), γE-γE-(O2Oc)-(O2Oc)-γE-γE (FIG. 2U), and (PEG)2-(PEG)2-γE (FIG. 2V). All linkers shown with the N-terminal on the left and C-terminal on right.

FIGS. 3A-3P are drawings depicting the exemplary non-natural amino acids 2-amino-2-methylpropanoic acid (Aib) (FIG. 3A), (S)-2-amino-2-methyl-3-phenylpropanoic acid (αMePhe) (FIG. 3B), (S)-2-amino-3-hydroxy-2-methylpropanoic acid (αMeSer) (FIG. 3C), D-glutamine (dGln) (FIG. 3D), β-dimethylglutamine (β-dimethylGln) (FIG. 3E), (S)-2,5-diamino-2-methyl-5-oxopentanoic acid (αMeGln) (FIG. 3F), D-serine (dSer) (FIG. 3G), methyl-L-glutamine (N-MeGln) (FIG. 3H), ((1H-imidazol-4-yl)methyl)glycine (NHis) (FIG. 3I), 1-aminocyclopropane-1-carboxylic acid (Acpr) (FIG. 3J), 1-aminocyclobutane-1-carboxylic acid (Acbu) (FIG. 3K), N⁶-acetyl-L-lysine (Ac-Lys) (FIG. 3L), (S)-2-amino-5-guanidino-3,3-dimethylpentanoic acid (β-dimethylArg) (FIG. 3M), (S)-2-amino-3,3-diphenylpropanoic acid (Dip) (FIG. 3N), (S)-2-amino-3-cyclohexylpropanoic acid (Cha) (FIG. 3O), (S)-2-aminohexanoic acid (Nle) (FIG. 3P), (S)-3-([1,1′-biphenyl]-4-yl)-2-aminopropanoic acid (Bip) (FIG. 3Q), 1-methyl-L-tryptophan (1-Methyl-Trp) (FIG. 3R), and (S)-2-amino-3-(5-bromo-1H-indol-3-yl)propanoic acid (5-Br-Trp) (FIG. 3S).

FIGS. 4A-4D are drawings depicting the structure of exemplary peptides: peptide 224 (FIG. 4A), peptide 229 (FIG. 4B), peptide 188 (FIG. 4C), and peptide 195 (FIG. 4D).

DETAILED DESCRIPTION OF THE INVENTION I. Definitions

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure is related. For example, the Concise Dictionary of Biomedicine and Molecular Biology, Juo, Pei-Show, 2nd ed., 2002, CRC Press; The Dictionary of Cell and Molecular Biology, 3rd ed., 1999, Academic Press; and the Oxford Dictionary Of Biochemistry And Molecular Biology, Revised, 2000, Oxford University Press, provide one of skill with a general dictionary of many of the terms used in this disclosure.

Units, prefixes, and symbols are denoted in their Système International de Unites (SI) accepted form. Numeric ranges are inclusive of the numbers defining the range. Unless otherwise indicated, amino acid sequences are written left to right in amino to carboxy orientation. The headings provided herein are not limitations of the various aspects of the disclosure, which can be had by reference to the specification as a whole. Accordingly, the terms defined immediately below are more fully defined by reference to the specification in its entirety.

Throughout this disclosure, the term “a” or “an” entity refers to one or more of that entity; for example, “a polynucleotide,” is understood to represent one or more polynucleotides. As such, the terms “a” (or “an”), “one or more,” and “at least one” can be used interchangeably herein.

Furthermore, “and/or” where used herein is to be taken as specific disclosure of each of the two specified features or components with or without the other. Thus, the term “and/or” as used in a phrase such as “A and/or B” herein is intended to include “A and B,” “A or B,” “A” (alone), and “B” (alone). Likewise, the term “and/or” as used in a phrase such as “A, B, and/or C” is intended to encompass each of the following aspects: A, B, and C; A, B, or C; A or C; A or B; B or C; A and C; A and B; B and C; A (alone); B (alone); and C (alone).

As used herein, the terms “about” and “approximately,” when used to modify a numeric value or numeric range, indicate that deviations of up to 10% above and down to 10% below the value or range remain within the intended meaning of the recited value or range. It is understood that wherever aspects are described herein with the language “about” or “approximately” a numeric value or range, otherwise analogous aspects referring to the specific numeric value or range are also provided.

It is understood that wherever aspects are described herein with the language “comprising,” otherwise analogous aspects described in terms of “consisting of” and/or “consisting essentially of” are also provided. A peptide “comprising” a particular amino acid sequence refers to a peptide containing the amino acid sequence, wherein the peptide may or may not contain additional amino acids or other modifications to the amino acid sequence. A peptide “consisting of” a particular amino acid sequence refers to a peptide containing only the amino acid sequence and no additional amino acids or other modifications to the amino acid sequence. A peptide “comprising” an amino acid sequence “consisting of” a particular amino acid sequence refers to a peptide containing the amino acid sequence and no additional amino acids; however, the peptide may comprise other modifications to the amino acid sequence (e.g., an acyl moiety or a palmitoyl moiety).

As used herein, the term “amino acid” refers to naturally occurring and non-natural amino acids, as well as amino acid analogs and amino acid mimetics that function in a manner similar to the naturally occurring amino acids. Naturally encoded amino acids are the 20 common amino acids (alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine) and pyrrolysine and selenocysteine. Amino acid analogs refers to compounds that have the same basic chemical structure as a naturally occurring amino acid, i.e., an a carbon that is bound to a hydrogen, a carboxyl group, an amino group, and an R group, such as, homoserine, norleucine, methionine sulfoxide, and methionine methyl sulfonium. Such analogs have modified R groups (such as, norleucine) or modified peptide backbones, but retain the same basic chemical structure as a naturally occurring amino acid.

A “non-natural amino acid” refers to an amino acid that is not one of the 20 common amino acids or pyrrolysine or selenocysteine; other terms that may be used synonymously with the term “non-natural amino acid” are “non-naturally encoded amino acid,” “unnatural amino acid,” “non-naturally-occurring amino acid,” and variously hyphenated and non-hyphenated versions thereof. The term “non-natural amino acid” includes, but is not limited to, amino acids that occur naturally by modification of a naturally encoded amino acid (including but not limited to, the 20 common amino acids or pyrrolysine and selenocysteine) but are not themselves incorporated into a growing polypeptide chain by the translation complex.

Examples of naturally-occurring amino acids that are not naturally-encoded include, but are not limited to, ((1H-imidazol-4-yl)methyl)glycine (NHis), S, 1-aminocyclobutane-1-carboxylic acid (1-aminocyclobutane-1-carboxylic acid; Acbu), 1-aminocyclopropane-1-carboxylic acid (1-aminocyclopropane-1-carboxylic acid; Acpr), Aminoisobutyric acid (2-amino-2-methylpropanoic acid; Aib), D-serine (dSer), αMethyl-Serine ((S)-2-amino-3-hydroxy-2-methylpropanoic acid (MeSer); (αMeSer), methyl-L-glutamine (N-MeGln), αMethyl-Glutamine ((S)-2,5-diamino-2-methyl-5-oxopentanoic acid; αMeGln), β-dimethylGln, αMethyl-Phenylalanine (S)-2-amino-2-methyl-3-phenylpropanoic acid; αMePhe), acetylated lysine N⁶-acetyl-L-lysine (Ac-Lys), Diphenylalanine ((S)-2-amino-3,3-diphenylpropanoic acid; Dip), β-dimethylarganine ((S)-2-amino-5-guanidino-3,3-dimethylpentaonic acid; β-dimethylArg), beta-cyclohexyl-L-alanine ((S)-2-amino-3-cyclohexylpropanoic acid; Cha), norleucine ((S)-2-aminohexanoic acid; Nle), D-glutamine (dGln) (S)-3-([1,1′-biphenyl]-4-yl)-2-aminopropanoic acid (Bip), 1-methyl-L-tryptophan (1-Methyl-Trp), and (S)-2-amino-3-(5-bromo-1H-indol-3-yl)propanoic acid (5-Br-Trp).

Amino acids may be referred to herein by either their commonly known three letter symbols or by the one-letter symbols recommended by the IUPAC-IUB Biochemical Nomenclature Commission. Nucleotides, likewise, may be referred to by their commonly accepted single-letter codes.

As used herein, the term “polypeptide” is intended to encompass a singular “polypeptide” as well as plural “polypeptides,” and comprises any chain or chains of two or more amino acids. Thus, as used herein, a “peptide,” a “peptide subunit,” a “protein,” an “amino acid chain,” an “amino acid sequence,” or any other term used to refer to a chain or chains of two or more amino acids, are included in the definition of a “polypeptide,” even though each of these terms can have a more specific meaning. The term “polypeptide” can be used instead of, or interchangeably with any of these terms. The term further includes polypeptides which have undergone post-translational or post-synthesis modifications, for example, conjugation of a palmitoyl group, glycosylation, acetylation, phosphorylation, amidation, derivatization by known protecting/blocking groups, proteolytic cleavage, or modification by non-naturally occurring amino acids.

More specifically, the term “peptide” as used herein encompasses full length peptides and fragments, variants or derivatives thereof, e.g., a GLP-1/glucagon agonist peptide (e.g., 29, 30, or 31 amino acids in length). A “peptide” as disclosed herein, e.g., a GLP-1/glucagon agonist peptide, can be part of a fusion polypeptide comprising additional components such as, e.g., an Fc domain or an albumin domain, to increase half-life. A peptide as described herein can also be derivatized in a number of different ways. A peptide described herein can comprise modifications including e.g., conjugation of a lipid including a palmitoyl group, stearoyl group, lauryl group, myristoyl group, margaroyl group, octadecanedioic acid (C18diacid), or icosanedioic acid (C20diacid). Exemplary lipids are provided in FIGS. 1A-1G.

A peptide described herein can comprise modifications including e.g., conjugation of a linker comprising 2-(2-(2-aminoethoxy)ethosy)acetic acid (O2Oc), PEG, and/or gammaglutamic acid (γE). In some aspects, a linker comprises 2-(2-(2-aminoethoxy)ethosy)acetic acid (O2Oc), (O2Oc)-(O2Oc), (O2Oc)-γE-(O2Oc), 3-(2-(2-aminoethoxy)ethoxy)propanoic acid) ((PEG)2), 1-amino-3,6,9,12-tetraoxapentadecan-15-oic acid ((PEG)4), 1-amino-3,6,9,12,15,18,21,14-octaoxaheptacosan-27-oic acid ((PEG)8), 1-amino-3,6,9,12,15,18,21,24,27,30,33,36-dodecaoxanonatriacontan-39-oic acid ((PEG)12), gammaglutamic acid (γE), (PEG)2-(PEG)2-γE-γE, (PEG)2-γE-(PEG)2-γE, γE-(O2Oc), γE-(O2Oc)-(O2Oc), γE-(O2Oc)-γE-(O2Oc), γE-(PEG)2-(PEG)2, γE-(PEG)2-γE-(PEG)2, γE-(PEG)4, γE-γE, (E-γE-(O2Oc), γE-γE-(O2Oc)-(O2Oc), γE-γE-(PEG)12, γE-γE-(PEG)2-(PEG)2, γE-γE-(PEG)2-γE-γE, γE-γE-(PEG)4, γE-γE-(PEG)8, γE-γE-(O2Oc)-(O2Oc)-γE-γE, and (PEG)2-(PEG)2-γE. Exemplary linkers are provided in FIGS. 2A-2V.

The term “isolated” refers to the state in which peptides or nucleic acids, will generally be in accordance with the present disclosure. Isolated peptides and isolated nucleic acids will be free or substantially free of material with which they are naturally associated such as other peptides or nucleic acids with which they are found in their natural environment, or the environment in which they are prepared (e.g. cell culture) when such preparation is by recombinant DNA technology practiced in vitro or in vivo. Peptides and nucleic acid can be formulated with diluents or adjuvants and still for practical purposes be isolated—for example the peptides will normally be mixed with gelatin or other carriers if used to coat microtiter plates for use in immunoassays, or will be mixed with pharmaceutically acceptable carriers or diluents when used in diagnosis or therapy.

A “recombinant” peptide refers to a peptide produced via recombinant DNA technology. Recombinantly produced peptides expressed in host cells are considered isolated for the purpose of the present disclosure, as are native or recombinant polypeptides which have been separated, fractionated, or partially or substantially purified by any suitable technique.

The terms “fragment,” “analog,” “derivative,” or “variant” when referring to a GLP-1/glucagon agonist peptide include any peptide which retains at least some desirable activity, e.g., binding to glucagon receptors and/or GLP-1 receptors. Fragments of GLP-1/glucagon agonist peptides provided herein include proteolytic fragments, deletion fragments which exhibit desirable properties during expression, purification, and or administration to a subject.

The term “variant,” as used herein, refers to a peptide that differs from the recited peptide due to amino acid substitutions, deletions, insertions, and/or modifications. Variants can be produced using art-known mutagenesis techniques. Variants can also, or alternatively, contain other modifications. For example, a peptide can be conjugated or coupled, e.g., fused to a heterologous amino acid sequence or other moiety, e.g., for increasing half-life, solubility, or stability. Examples of moieties to be conjugated or coupled to a peptide provided herein include, but are not limited to, albumin, an immunoglobulin Fc region, polyethylene glycol (PEG), and the like. The peptide can also be conjugated or produced coupled to a linker or other sequence for ease of synthesis, purification or identification of the peptide (e.g., 6-His), or to enhance binding of the polypeptide to a solid support.

The terms “composition” or “pharmaceutical composition” refer to compositions containing a GLP-1/glucagon agonist peptide provided herein, along with e.g., pharmaceutically acceptable carriers, excipients, or diluents for administration to a subject in need of treatment, e.g., a human subject in need of improved glycemic control, weight loss, treatment of Type 2 Diabetes Mellitus, and/or treatment of NASH.

The term “pharmaceutically acceptable” refers to compositions that are, within the scope of sound medical judgment, suitable for contact with the tissues of human beings and animals without excessive toxicity or other complications commensurate with a reasonable benefit/risk ratio.

An “effective amount” is that amount of an agent provided herein (e.g., a GLP-1/glucagon agonist peptide), the administration of which to a subject, either in a single dose or as part of a series, is effective for treatment, e.g., for improved glycemic control, weight loss, treatment of Type 2 Diabetes Mellitus, and/or treatment of NASH.

As used herein, the terms “subject” and “patient” are used interchangeably. The subject can be an animal. In some aspects of the present disclosure, the subject is a mammal such as a non-human animal (e.g., cow, pig, horse, cat, dog, rat, mouse, monkey or other primate, etc.). In some aspects of the present disclosure, the subject is a cynomolgus monkey. In some aspects of the present disclosure, the subject is a human.

As used herein, a “subject in need thereof” or a “patient in need thereof” refers to an individual for whom it is desirable to treat, e.g., a subject in need of improved glycemic control, weight loss, treatment of Type 2 Diabetes Mellitus, and/or treatment of NASH.

Terms such as “treating” or “treatment” or “to treat” refer to therapeutic measures that cure and/or halt progression of a diagnosed pathologic condition or disorder. Terms such as “preventing” refer to prophylactic or preventative measures that prevent and/or slow the development of a targeted pathologic condition or disorder. Thus, those in need of treatment include those already with the disease or condition. Those in need of prevention include those prone to have the disease or condition and those in whom the disease or condition is to be prevented.

Terms such as “decreasing the severity” refer to therapeutic measures that slow down or lessen the symptoms of a diagnosed pathologic condition or disorder.

As used herein, a “GLP-1 agonist peptide” is a peptide that is not native GLP-1 but exhibits activity at the GLP-1 receptor of about at least 1% or more relative to native GLP-1, under the conditions of the cAMP assay (see Example 2). In some aspects, a GLP-1 agonist peptide exhibits activity at the GLP-1 receptor of at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or more relative to native GLP-1, under the conditions of the cAMP assay (see Example 2).

As used herein, a “glucagon agonist peptide” is a peptide that is not native glucagon but exhibits activity at the glucagon receptor of at least 1%, or more relative to native glucagon, under the conditions of the cAMP assay (see Example 2). In some aspects, a glucagon agonist peptide exhibits activity at the glucagon receptor of at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or more relative to native GLP-1, under the conditions of the cAMP assay (see Example 2).

As used herein a “GLP-1/glucagon agonist peptide,” “GLP-1/glucagon coagonist peptide,” “GLP-1 and glucagon dual agonist peptide” or “GLP-1 and glucagon dual coagonist peptide” is a peptide that it not native GLP-1 and is not native glucagon that exhibits activity at the glucagon receptor of at least 1% or more relative to native glucagon and also exhibits activity at the GLP-1 receptor of about at least 1% or more relative to native GLP-1, under the conditions of the cAMP assay (see Example 2). In some aspects, a “GLP-1/glucagon agonist peptide” or a “GLP-1 and glucagon dual agonist peptide” exhibits activity at the glucagon receptor of at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or more relative to native glucagon and also exhibits activity at the GLP-1 receptor of about at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or more relative to native GLP-1, under the conditions of the cAMP assay (see Example 2).

As used herein, term “relative potency ratio” refers to the % GLP-1R activity relative to GLP-1/% GlucR activity relative to glucagon.

As used herein the term “native glucagon” refers to naturally-occurring glucagon, e.g., human glucagon, comprising the sequence of SEQ ID NO: 1. The term “native GLP-1” refers to naturally-occurring GLP-1, e.g., human GLP-1, and is a generic term that encompasses, e.g., GLP-1(7-36) amide (SEQ ID NO: 2), GLP-1(7-37) acid (SEQ ID NO: 3), or a mixture of those two compounds. As used herein, a general reference to “glucagon” or “GLP-1” in the absence of any further designation is intended to mean native human glucagon or native human GLP-1, respectively. Unless otherwise indicated, “glucagon” refers to human glucagon, and “GLP-1” refers to human GLP-1.

The term “sequence identity” as used herein refers to a relationship between two or more polynucleotide sequences or between two or more polypeptide sequences. When a position in one sequence is occupied by the same nucleic acid base or amino acid in the corresponding position of the comparator sequence, the sequences are said to be “identical” at that position. The percentage “sequence identity” is calculated by determining the number of positions at which the identical nucleic acid base or amino acid occurs in both sequences to yield the number of “identical” positions. The number of “identical” positions is then divided by the total number of positions in the comparison window and multiplied by 100 to yield the percentage of “sequence identity.” Percentage of “sequence identity” is determined by comparing two optimally aligned sequences over a comparison window. In order to optimally align sequences for comparison, the portion of a polynucleotide or polypeptide sequence in the comparison window can comprise additions or deletions termed gaps while the reference sequence is kept constant. An optimal alignment is that alignment which, even with gaps, produces the greatest possible number of “identical” positions between the reference and comparator sequences. Percentage “sequence identity” between two sequences can be determined using the version of the program “BLAST 2 Sequences” which was available from the National Center for Biotechnology Information as of Sep. 1, 2004, which program incorporates the programs BLASTN (for nucleotide sequence comparison) and BLASTP (for polypeptide sequence comparison), which programs are based on the algorithm of Karlin and Altschul (Proc. Natl. Acad. Sci. USA 90(12):5873-5877, 1993). When utilizing “BLAST 2 Sequences,” parameters that were default parameters as of Sep. 1, 2004, can be used for word size (3), open gap penalty (11), extension gap penalty (1), gap drop-off (50), expect value (10), and any other required parameter including but not limited to matrix option.

Glucagon (SEQ ID NO: 1) HSQGTFTSDYSKYLDSRRAQDFVQWLMNT-acid GLP-1(7-36) amide (SEQ ID NO: 2) HAEGTFTSDVSSYLEGQAAKEFIAWLVKGR-amide GLP-1(7-37) acid (SEQ ID NO: 3) HAEGTFTSDVSSYLEGQAAKEFIAWLVKGRG-acid

II. GLP-1/Glucagon Agonist Peptides

Provided herein are peptides that bind both to a glucagon receptor and to a GLP-1 receptor. In some aspects, the peptides provided herein are co-agonists (dual agonists) of glucagon and GLP-1 activity. Such peptides are referred to herein as GLP-1/glucagon agonist peptides. In some aspects, GLP-1/glucagon agonist peptides as provided herein are active at the human GLP1 and human glucagon receptors.

In certain aspects, GLP-1/glucagon agonist peptides provided herein exhibit in vitro potencies at the GLP-1 receptor as shown by an EC50 in the cAMP assay (see Example 2) of less than 10,000 pM, less than 5000 pM, less than 2500 pM, less than 1000 pM, less than 900 pM, less than 800 pM, less than 700 pM, less than 600 pM, less than 500 pM, less than 400 pM, less than 300 pM, less than 200 pM, less than 100 pM, less than 50 pM, less than 25 pM, less than 20 pM, less than 15 pM, less than 10 pM, less than 5 pM, less than 4 pM, less than 3 pM, or less than 2 pM.

In certain aspects, GLP-1/glucagon agonist peptides provided herein exhibit in vitro potencies at the glucagon receptor as shown by an EC50 in the cAMP assay (see Example 2) of less than 10,000 pM, less than 5000 pM, less than 2500 pM, less than 1000 pM, less than 900 pM, less than 800 pM, less than 700 pM, less than 600 pM, less than 500 pM, less than 400 pM, less than 300 pM, less than 200 pM, less than 100 pM, less than 50 pM, less than 25 pM, less than 20 pM, less than 15 pM, less than 10 pM, less than 5 pM, less than 4 pM, less than 3 pM, or less than 2 pM.

In certain aspects, GLP-1/glucagon agonist peptides provided herein have a hGLP-1R/hGCGR relative potency ratio of about 1 to about 25. In certain aspects, GLP-1/glucagon agonist peptides provided herein have a hGLP-1R/hGCGR relative potency ratio of about 1 to about 20. In certain aspects, GLP-1/glucagon agonist peptides provided herein have a hGLP-1R/hGCGR relative potency ratio of about 1 to about 15. In certain aspects, GLP-1/glucagon agonist peptides provided herein have a hGLP-1R/hGCGR relative potency ratio of about 1 to about 10.

In certain aspects, GLP-1/glucagon agonist peptides provided herein have a hGLP-1R/hGCGR relative potency ratio of about 2 to about 25. In certain aspects, GLP-1/glucagon agonist peptides provided herein have a hGLP-1R/hGCGR relative potency ratio of about 2 to about 20. In certain aspects, GLP-1/glucagon agonist peptides provided herein have a hGLP-1R/hGCGR relative potency ratio of about 2 to about 15. In certain aspects, GLP-1/glucagon agonist peptides provided herein have a hGLP-1R/hGCGR relative potency ratio of about 2 to about 10.

In certain aspects, GLP-1/glucagon agonist peptides provided herein, when administered to mice at 10 nmol/kg (as performed in Example 3) reduce 24-hour food intake by at least 10/6 relative to mice treated with a vehicle control. In certain aspects, GLP-1/glucagon agonist peptides provided herein, when administered to mice at 10 nmol/kg (as performed in Example 3) reduce 24-hour food intake by at least 20% relative to mice treated with a vehicle control. In certain aspects, GLP-1/glucagon agonist peptides provided herein, when administered to mice at 10 nmol/kg (as performed in Example 3) reduce 24-hour food intake by at least 30% relative to mice treated with a vehicle control.

In certain aspects, GLP-1/glucagon agonist peptides provided herein, when administered to mice at 10 nmol/kg (as performed in Example 3) reduce 24-hour food intake by at 10-70% relative to mice treated with a vehicle control. In certain aspects, GLP-1/glucagon agonist peptides provided herein, when administered to mice at 10 nmol/kg (as performed in Example 3) reduce 24-hour food intake by at least 20% or by 20-70% relative to mice treated with a vehicle control. In certain aspects, GLP-1/glucagon agonist peptides provided herein, when administered to mice at 10 nmol/kg (as performed in Example 3) reduce 24-hour food intake by at least 30% or by 30-70% relative to mice treated with a vehicle control.

In certain aspects, GLP-1/glucagon agonist peptides provided herein are stable. For example, in certain aspects, GLP-1/glucagon agonist peptides provided herein stable in the presence of FasSSGF (fasted state simulated gastric fluid) such that at least 25% of the GLP-1/glucagon agonist peptide remains intact after incubation with FasSSGF for 30 minutes (as performed in Example 4.) In certain aspects, GLP-1/glucagon agonist peptides provided herein stable in the presence of FasSSGF such that at least 40% of the GLP-1/glucagon agonist peptide remains intact after incubation with FasSSGF for 30 minutes (as performed in Example 4.) In certain aspects, GLP-1/glucagon agonist peptides provided herein stable in the presence of FasSSGF such that at least 50% of the GLP-1/glucagon agonist peptide remains intact after incubation with FasSSGF for 30 minutes (as performed in Example 4.) In certain aspects, GLP-1/glucagon agonist peptides provided herein stable in the presence of FasSSGF such that at least 60% of the GLP-1/glucagon agonist peptide remains intact after incubation with FasSSGF for 30 minutes (as performed in Example 4.) In certain aspects, GLP-1/glucagon agonist peptides provided herein stable in the presence of FasSSGF such that at least 70% of the GLP-1/glucagon agonist peptide remains intact after incubation with FasSSGF for 30 minutes (as performed in Example 4.)

In certain aspects, GLP-1/glucagon agonist peptides provided herein stable in the presence of neprilysin such that at least 55% of the GLP-1/glucagon agonist peptide remains intact after incubation with neprilysin for 24 hours (as performed in Example 5.) In certain aspects, GLP-1/glucagon agonist peptides provided herein stable in the presence of neprilysin such that at least 60% of the GLP-1/glucagon agonist peptide remains intact after incubation with neprilysin for 24 hours (as performed in Example 5.) In certain aspects, GLP-1/glucagon agonist peptides provided herein stable in the presence of neprilysin such that at least 65% of the GLP-1/glucagon agonist peptide remains intact after incubation with neprilysin for 24 hours (as performed in Example 5.) In certain aspects, GLP-1/glucagon agonist peptides provided herein stable in the presence of neprilysin such that at least 70% of the GLP-1/glucagon agonist peptide remains intact after incubation with neprilysin for 24 hours (as performed in Example 5.) In certain aspects, GLP-1/glucagon agonist peptides provided herein stable in the presence of neprilysin such that at least 75% of the GLP-1/glucagon agonist peptide remains intact after incubation with neprilysin for 24 hours (as performed in Example 5.) In certain aspects, GLP-1/glucagon agonist peptides provided herein stable in the presence of neprilysin such that at least 80% of the GLP-1/glucagon agonist peptide remains intact after incubation with neprilysin for 24 hours (as performed in Example 5.) In certain aspects, GLP-1/glucagon agonist peptides provided herein stable in the presence of neprilysin such that at least 85% of the GLP-1/glucagon agonist peptide remains intact after incubation with neprilysin for 24 hours (as performed in Example 5.) In certain aspects, GLP-1/glucagon agonist peptides provided herein stable in the presence of neprilysin such that at least 90% of the GLP-1/glucagon agonist peptide remains intact after incubation with neprilysin for 24 hours (as performed in Example 5.) In certain aspects, GLP-1/glucagon agonist peptides provided herein stable in the presence of neprilysin such that at least 95% of the GLP-1/glucagon agonist peptide remains intact after incubation with neprilysin for 24 hours (as performed in Example 5.)

In certain aspects, GLP-1/glucagon agonist peptides provided herein are stable. For example, in certain aspects, GLP-1/glucagon agonist peptides provided herein stable in the presence of FasSSIF (fasted state simulated intestinal fluid)/Pancreatin such that at least 10% of the GLP-1/glucagon agonist peptide remains intact after incubation with FasSSIF/Pancreatin for 30 minutes (as performed in Example 6.) In certain aspects, GLP-1/glucagon agonist peptides provided herein are stable. For example, in certain aspects, GLP-1/glucagon agonist peptides provided herein stable in the presence of FasSSIF/Pancreatin such that at least 20% of the GLP-1/glucagon agonist peptide remains intact after incubation with FasSSIF/Pancreatin for 30 minutes (as performed in Example 6.) In certain aspects, GLP-1/glucagon agonist peptides provided herein are stable. For example, in certain aspects, GLP-1/glucagon agonist peptides provided herein stable in the presence of FasSSIF/Pancreatin such that at least 25% of the GLP-1/glucagon agonist peptide remains intact after incubation with FasSSIF/Pancreatin for 30 minutes (as performed in Example 6.) In certain aspects, GLP-1/glucagon agonist peptides provided herein are stable. For example, in certain aspects, GLP-1/glucagon agonist peptides provided herein stable in the presence of FasSSIF/Pancreatin such that at least 50% of the GLP-1/glucagon agonist peptide remains intact after incubation with FasSSIF/Pancreatin for 30 minutes (as performed in Example 6.) In certain aspects, GLP-1/glucagon agonist peptides provided herein are stable. For example, in certain aspects, GLP-1/glucagon agonist peptides provided herein stable in the presence of FasSSIF/Pancreatin such that at least 75% of the GLP-1/glucagon agonist peptide remains intact after incubation with FasSSIF/Pancreatin for 30 minutes (as performed in Example 6.) In certain aspects, GLP-1/glucagon agonist peptides provided herein are stable. For example, in certain aspects, GLP-1/glucagon agonist peptides provided herein stable in the presence of FasSSIF/Pancreatin such that at least 80% of the GLP-1/glucagon agonist peptide remains intact after incubation with FasSSIF/Pancreatin for 30 minutes (as performed in Example 6.) In certain aspects, GLP-1/glucagon agonist peptides provided herein are stable. For example, in certain aspects, GLP-1/glucagon agonist peptides provided herein stable in the presence of FasSSIF/Pancreatin such that at least 90% of the GLP-1/glucagon agonist peptide remains intact after incubation with FasSSIF/Pancreatin for 30 minutes (as performed in Example 6.)

A GLP-1/glucagon agonist peptide as disclosed herein can comprise a heterologous moiety, e.g., to extend half-life. The heterologous moiety can be a protein, a peptide, a protein domain, a linker, an organic polymer, an inorganic polymer, a polyethylene glycol (PEG), biotin, an albumin, a human serum albumin (HSA), a HSA FcRn binding portion, an antibody, a domain of an antibody, an antibody fragment, a single chain antibody, a domain antibody, an albumin binding domain, an enzyme, a ligand, a receptor, a binding peptide, a non-FnIII scaffold, an epitope tag, a recombinant polypeptide polymer, a cytokine, and a combination of two or more of such moieties.

In some aspects, a GLP-1/glucagon agonist peptide as disclosed herein binds to a GLP-1 receptor (GLP-1R), binds to a glucagon receptor (GCGR), or binds to both a GLP-1R and a GCGR. In some aspects, the GLP-1R is human GLP-1R. In some aspects, the GCGR is human GCGR. In some aspects, the peptide is an agonist of GLP-1 activity, an agonist of glucagon activity, or an agonist of both GLP-1 and glucagon activity.

In some aspects, a GLP-1/glucagon agonist peptide as disclosed herein has increased proteolytic-resistance relative to the natural ligand of the GLP-1R and/or GCGR. In some aspects, a GLP-1/glucagon agonist peptide as disclosed herein has increased proteolytic-resistance relative to cotadutide (SEQ ID NO: 358). In some aspects, a GLP-1/glucagon agonist peptide as disclosed herein has increased proteolytic-resistance relative to semaglutide (SEQ ID NO. 359). In some aspects, a GLP-1/glucagon agonist peptide as disclosed herein has increased proteolytic-resistance relative to cotadutide (SEQ ID NO: 358) and semaglutide (SEQ ID NO: 359).

In some aspects, a GLP-1/glucagon agonist peptide provided herein comprises the sequence: X1-X2-X3-G-X5-X6-T-S-D-X10-S-X12-X13-L-X15-X16-X17-X18-X19-X20-X21-X22-X23-X24-X25-X26-X27-X28-X29-X30-X31-Z, wherein X1 is H or NHis, X2 is S, 1-aminocyclobutane-1-carboxylic acid (Acbu), 1-aminocyclopropane-1-carboxylic acid (Acpr), Aminoisobutyric acid (Aib), D-serine (dSer), or αMethyl-Serine (αMeSer), X3 is Q, H, I, D-glutamine (dGln), methyl-L-glutamine (N-MeGln), α-Methyl-glutamine (αMeGln), or β-dimethylglutamine (β-dimethylGln), X5 is T or S, X6 is F or αMethyl-Phenylalanine (αMePhe), X10 is Y, K, or V, wherein the K can comprise an acyl moiety and/or can be lipidated, X12 is K, acetylated lysine (Ac-Lys), E, or R, X13 is Y, Aib, αMethyl-Phenylalanine (αMePhe), Diphenylalanine (Dip), I, or K, wherein the K can comprise an acyl moiety and/or can be lipidated, X15 is D or E, X16 is S, Aib, E, T, R, A, K, L, or V, X17 is R, E, K, Q, or β-dimethylarganine (β-dimethylArg), wherein the K can comprise an acyl moiety and/or can be lipidated, X18 is R, A, Aib, Q, S, or β-dimethylArg, X19 is A or V, X20 is Q, Aib, E, K, L, or R, wherein the K can comprise an acyl moiety and/or can be lipidated, X21 is D, E, or L, X22 is F, I, or αMePhe, X23 is V or I, X24 is Q, A, E, K, L, or R, wherein the K can comprise an acyl moiety and/or can be lipidated, X25 is W, Aib, Dip, H, I, S, biphenyl-alanine (Bip), 1-methyl tryptophan (1-Methyl-Trp), 5-Bromo tryptophan (5-BrTrp), or αMePhe, X26 is L, beta-cyclohexyl-L-alanine (Cha), I, or V, X27 is M, A, E, I, L, norleucine (Nle), S, K, or V, X28 is N, (PEG)4, A, Aib, E, G, R, S, or not present, X29 is T, Aib, E, G, A, R, or not present, X30 is not present, E, A, Aib, K, T, or G, X31 is not present, I, or G, and Z is amide or acid (SEQ ID NO: 4), wherein the peptide does not comprise SEQ ID NO: 1 and does not comprise HSQGTFTSDX10SEYLDSERARDFVAWLEAGG-acid, wherein X10=Lys[ε-γE-Palmitoyl](SEQ ID NO: 538). In some aspects, X2 is Aib and/or X10 is V. In some aspects, X3 is Q, X15 is D, X18 is R, X20 is R, X21 is D, X23 is V, and/or X30 is G. In some aspects, X13 is αMePhe, X16 is T, X17 is K, X27 is L, X28 is E, and/or X29 is Aib.

In some aspects, the residue at position 10, 13, 17, 20, or 24 is acylated. In some aspects, the residue at position 10, 13, 17, 20, or 24 is lipidated. In some aspects, the lipid is selected from the group consisting of a palmitoyl group, stearoyl group, lauryl group, myristoyl group, margaroyl group, arachidoyl group, octadecanedioic acid (C18diacid), and icosanedioic acid (C20diacid).

In some aspects, the lipid attached to the residue at position 10, 13, 17, 20, or 24 is attached via a linker. In some aspects, the linker is selected from the group consisting of (O2Oc), (O2Oc)-(O2Oc), (O2Oc)-γE-(O2Oc), (PEG)2-(PEG)2-γE-γE, (PEG)2-γE-(PEG)2-γE, γE, γE-(O2Oc), γE-(O2Oc)-(O2Oc), γE-(O2Oc)-γE-(O2Oc), γE-(PEG)2-(PEG)2, γE-(PEG)2-γE-(PEG)2, γE-(PEG)4, γE-γE, γE-γE-(O2Oc), γE-γE-(O2Oc)-(O2Oc), γE-γE-(PEG)12, γE-γE-(PEG)2-(PEG)2, γE-γE-(PEG)2-γE-γE, γE-γE-(PEG)4, (PEG)2-(PEG)2-γE, γE-γE-(O2Oc)-(O2Oc)-γE-γE, and γE-γE-(PEG)8.

In some aspects, the linker is linked to the epsilon amino group of the residue at position 10, 13, 17, 20, and/or 24.

In some aspects, the peptide comprises any one of SEQ ID NOs: 6-411 and 418-537. In some aspects, the peptide comprises SEQ ID NO: 99. In some aspects, the peptide comprises SEQ ID NO: 106. In some aspects, the peptide comprises SEQ ID NO: 228. In some aspects, the peptide comprises SEQ ID NO: 233.

In some aspects, the peptide comprises the sequence: H-X2-X3-G-X5-X6-T-S-D-X10-S-X12-X13-L-X15-X16-X17-X18-A-X20-D-X22-X23-X24-X25-X26-X27-X28-X29-X30-X31-Z, wherein X2 is S, Aminoisobutyric acid (Aib), or αMethyl-Serine (αMeSer), X3 is Q or H, X5 is T or S, X6 is F or αMethyl-Phenylalanine (αMePhe), X10 is Y or V, X12 is K or acetylated lysine (Ac-Lys), X13 is Y, αMePhe, Aib, Diphenylalanine (Dip), or I, X15 is D or E, X16 is S, T, A, E, K, L, R, or V, X17 is R or K, wherein the K can comprise an acyl moiety and/or can be lipidated, X18 is R, A, Q, or β-dimethylarganine (β-dimethylArg), X20 is Q, R, Aib, L, or E, X22 is F, I, or αMePhe, X23 is V or I, X24 is Q, E, A, L, or R, X25 is W, Aib, S, Dip, I, H, biphenyl-alanine (Bip), 1-methyl tryptophan (1-Methyl-Trp), 5-Bromo tryptophan (5-BrTrp), or αMePhe, X26 is L, I, or beta-cyclohexyl-L-alanine (Cha) or V, X27 is M, A, L, E, V, I, K, norleucine (Nle), or S, X28 is N, Aib, E, (PEG)4, A, S, or G, X29 is T, not present, Aib, G, A, R, or E, X30 is not present. G, A, Aib, K, or E, X31 is not present, and Z is amide or acid (SEQ ID NO: 5), wherein the peptide does not comprise SEQ ID NO: 1.

In some aspects, the residue at position 17 is acylated. In some aspects, the residue at position 17 is lipidated. In some aspects, the lipid is selected from the group consisting of a palmitoyl group, stearoyl group, lauryl group, myristoyl group, margaroyl group, arachidoyl group, octadecanedioic acid (C18diacid), and icosanedioic acid (C20diacid).

In some aspects, the lipid attached to the residue at position 17 is attached via a linker. In some aspects, the linker is selected from the group consisting of (O2Oc), (O2Oc)-(O2Oc), (O2Oc)-γE-(O2Oc), (PEG)2-(PEG)2-γE-γE, (PEG)2-γE-(PEG)2-γE, γE, γE-(O2Oc), γE-(O2Oc)-(O2Oc), γE-(O2Oc)-γE-(O2Oc), γE-(PEG)2-(PEG)2, γE-(PEG)2-γE-(PEG)2, γE-(PEG)4, γE-γE, γE-γE-(O2Oc), γE-γE-(O2Oc)-(O2Oc), γE-γE-(PEG)12, γE-γE-(PEG)2-(PEG)2, γE-γE-(PEG)2-γE-γE, γE-γE-(PEG)4, and γE-γE-(PEG)8. In some aspects, the linker is selected from the group consisting of γE-γE-(O2Oc)-(O2Oc)-γE-γE, (O2Oc)-(O2Oc), γE, γE-(O2Oc)-(O2Oc), γE-γE-(O2Oc)-(O2Oc), γE-γE-(PEG)4, γE-γE-(PEG)2-(PEG)2, γE-γE-(PEG)8, γE-γE-(PEG)12, (PEG)2-(PEG)2-γE-γE, (PEG)2-γE-(PEG)2-γE, γE-(PEG)2-γE-(PEG)2, γE-(PEG)2-(PEG)2, (PEG)2-(PEG)2-γE, and γE-(PEG)4.

In some aspects, the linker is linked to the epsilon amino group of the residue at position 17.

In some aspects, the peptide comprises the sequence: H-Aminoisobutyric acid (Aib)-Q-G-T-X6-T-S-D-V-S-K-αMethyl-Phenylalanine (αMePhe)-L-X15-X16-K-X18-A-X20-X21-X22-X23-X24-W-X26-X27-X28-X29-X30-X31-Z, wherein X6 is F or αMethyl-Phenylalanine (αMePhe), X15 is E or D, X16 is T, S, K, E, A, L, or R, X18 is R or A, X20 is R, Q, or L, X21 is D or E, X22 is F or αMePhe, X23 is V or I, X24 is R, A, Q, or L, X25 is W, αMePhe biphenyl-alanine (Bip), 1-methyl tryptophan (1-Methyl-Trp), 5-Bromo tryptophan (5-BrTrp), or Aib, X26 is L, I, or V, X27 is L, A, E, V, I, or K, X28 is E, S, A, Aib, not present, or R, X29 is G, Aib, R, T, E, A, or not present, X30 is G, Aib, E, A, K, or not present, X31 is I or not present, and or G, and Z is amide or acid (SEQ ID NO: 412).

In some aspects, the lysine at position 17 is acylated. In some aspects, the lysine at position 17 is lipidated. In some aspects, the lipid is selected from the group consisting of a palmitoyl group, stearoyl group, lauryl group, myristoyl group, margaroyl group, arachidoyl group, octadecanedioic acid (C18diacid), and icosanedioic acid (C20diacid). In some aspects, the lipid is selected from the group consisting of octadecanedioic acid (C18diacid) and icosanedioic acid (C20diacid). In some aspects, the lipid is a octadecanedioic acid (C18diacid). In some aspects, the lipid is an icosanedioic acid (C20diacid).

In some aspects, the lipid is linked to the lysine at position 17 via a linker. In some aspects, the linker is selected from the group consisting of (O2Oc), (O2Oc)-(O2Oc), (O2Oc)-γE-(O2Oc), (PEG)2-(PEG)2-γE-γE, (PEG)2-γE-(PEG)2-γE, γE, γE-(O2Oc), γE-(O2Oc)-(O2Oc), γE-(O2Oc)-γE-(O2Oc), γE-(PEG)2-(PEG)2, γE-(PEG)2-γE-(PEG)2, γE-(PEG)4, γE-γE, γE-γE-(O2Oc), γE-γE-(O2Oc)-(O2Oc), γE-γE-(PEG)12, γE-γE-(PEG)2-(PEG)2, γE-γE-(PEG)2-γE-γE, γE-γE-(PEG)4, PEG)2-(PEG)2-γE, γE-γE-(O2Oc)-(O2Oc), and γE-γE-(PEG)8. In some aspects, the peptide of claim X, wherein the linker is selected from the group consisting of (PEG)2-(PEG)2-γE, (O2Oc)-(O2Oc), γE, γE-(O2Oc)-(O2Oc), γE-γE-(O2Oc)-(O2Oc), and γE-γE(O2Oc)-(O2Oc)-γE-γE. In some aspects, the linker is γE-(O2Oc)-(O2Oc).

In some aspects, the linker is linked to the epsilon amino group of the residue at position 17.

In certain aspects, GLP-1/glucagon agonist peptides as disclosed have desirable potencies at the glucagon and GLP-1 receptors, and have desirable relative potencies for promoting weight loss.

In some aspects, the peptide has the sequence of any one of SEQ ID NOs: 6-206 and 418-531. In some aspects, the peptide comprises SEQ ID NO: 99. In some aspects, the peptide comprises SEQ ISA NO: 106.

In some aspects, the peptide has the structure of any one of the structures depicted in FIGS. 4C-4D. In some aspects, the peptide has the structure of FIG. 4C. In some aspects, the peptide has the structure of FIG. 4D.

In some aspects, the peptide is any one of the peptides in Table 1.

TABLE 1 Peptides Modified at Position 17 Linker Sequence Albumin (described modification SEQ ID binding N→C Acylation C- with respect Peptide Sequence NO moiety term.) site term. to glucagon. Peptide HSQGS(αMePhe)TSDVS 6 C18diacid γE- 17 Amide 5S, 1 K(Aib)LDSK(O2Oc- (O2Oc)- 6αMePhe, O2Oc-γE- (O2Oc) 10V, 13Aib, C18diacid)17AAQD 17K, 18A, (αMePhe)VQ(Aib)IAN- 22αMePhe, amide 25Aib, 26I, 27A, des29T Peptide HSQGS(αMePhe)TSDVS 7 C20diacid γE- 17 Amide 5S 2 K(αMePhe)LDSK(O2Oc- (O2Oc)- 6αMePhe, O2Oc-γE- (O2Oc) 10V, C20diacid)17AAQD 13αMePhe, (αMePhe)VQWIANT-amide 17K, 18A, 22QMePhe, 26I, 27A Peptide HSQGS(αMePhe)TSDVS 8 C18diacid γE 17 Amide 5S, 3 K(αMePhe)LDSK(γE- 6αMePhe, C18diacid)17AAQDFVQ 10V, WIANT-amide 13αMePhe, 17K, 18A, 26I, 27A Peptide HSQGS(αMePhe)TSDVS 9 C18diacid γE- 17 Amide 5S, 4 K(αMePhe)LDSK(O2OC- (O2Oc)- 6αMePhe, O2Oc-γE- (O2Oc) 10V, C18diacid)17AAQDFVQ 13αMePhe, WIANT-amide 17K, 18A, 26I, 27A Peptide H(Aib)QGS(αMePhe)TS 10 C18diacid γE-γE- 17 Amide 2Aib, 5S, 5 DVSK(αMePhe)LDSK (O2Oc)- 6αMePhe, (O2Oc-O2Oc-γE-γE- (O2Oc) 10V, C18diacid)17AAQD 13αMePhe, (αMePhe)VQ(Aib)IAN- 17K, 18A, amide 22αMePhe, 25Aib, 26I, 27A, des29T Peptide H(Aib)HGS(αMePhe)TS 11 C18diacid γE- 17 Amide 2Aib, 3H, 5S, 6 DVSK(αMePhe)LDSK (O2Oc)- 6QMePhe, (O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)17AAQD 13αMePhe, (αMePhe)VEWIAN-amide 17K, 18A, 22αMePhe, 24E, 26I, 27A, des29T Peptide H(Aib)HGS(αMePhe)TS 12 C18diacid γE 17 Amide 2Aib, 3H, 5S, 7 DVSK(αMePhe)LDSK(γE- 6αMePhe, C18diacid)17AAQD 10V, (αMePhe)VEWIANT-amide 13αMePhe, 17K, 18A, 22αMePhe, 24E, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 13 C18diacid γE- 17 Amide 2Aib, 3H, 5S, 8 DVSK(αMePhe)LDSK (O2Oc)- 6αMePhe, (O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)17AAQDFVQ 13αMePhe, WIANT-amide 17K, 18A 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 14 C18diacid γE- 17 Amide 2Aib, 3H, 5S, 9 DVSK(αMePhe)LDSK (O2Oc)- 6αMePhe, (O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)17AARDFVQ 13αMePhe, WIANT-amide 17K, 18A, 20R, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 15 C18diacid γE- 17 Amide 2Aib, 3H, 5S, 10 DVSK(αMePhe)LDSK (O2Oc)- 6αMePhe, (O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)17AARDFVE 13αMePhe, WIANT-amide 17K, 18A, 20R, 24E, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 16 C18diacid γE- 17 Amide 2Aib, 3H, 5S, 11 DVSK(αMePhe)LDSK (O2Oc)- 6αMePhe, (O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)17AAQDFVQ 13αMePhe, (Aib)IANT-amide 17K, 18A, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 17 C18diacid γE- 17 Amide 2Aib, 3H, 5S, 12 DVSK(αMePhe)LDSK (O2Oc)- 6αMePhe, (O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)17AARDFVQ 13αMePhe, (Aib)IANT-amide 17K, 18A, 20R, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 18 C18diacid γE- 17 Amide 2Aib, 3H, 5S, 13 DVSK(αMePhe)LDSK (O2Oc)- 6αMePhe, (O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)17AARD 13αMePhe, (αMePhe)VQ(Aib)IANT- 17K, 18A, amide 20R, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 19 C20diacid γE-γE- 17 Amide 2Aib, 3H, 5S, 14 DVSK(αMePhe)LDSK (O2Oc)- 6αMePhe, (O2Oc2-VE2- (O2Oc) 10V, C20diacid)17AARD 13αMePhe, (αMePhe)VQ(Aib)IANT- 17K, 18A, amide 20R, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 20 C18diacid γE- 17 Amide 2Aib, 3H, 5S, 15 DVSK(αMePhe)LDSK (O2Oc)- 6αMePhe, (O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)17AARD 13αMePhe, (αMePhe)VE(Aib)IANT- 17K, 18A, amide 20R, 22αMePhe, 24E, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 21 C18diacid γE- 17 Amide 2Aib, 3H, 5S, 16 DVSK(αMePhe)LDSK (O2Oc)- 6αMePhe, (O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)17AARD 13αMePhe, (αMePhe)IA(Aib)IANT- 17K, 18A, amide 20R, 22αMePhe, 23I, 24A, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 22 C18diacid γE- 17 Amide 2Aib, 3H, 5S, 17 DVSK(αMePhe)LDSK (O2Oc)- 60MePhe, (O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)17AARD 13αMePhe, (αMePhe)VESIANT-amide 17K, 18A, 20R, 22αMePhe, 24E, 25S, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 23 C18diacid γE- 17 Amide 2Aib, 3H, 5S, 18 DVSK(αMePhe)LDSK (O2Oc)- 6αMePhe, (O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)17AARD 13αMePhe, (αMePhe)VQSIANT-amide 17K, 18A, 20R, 22αMePhe, 25S, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 24 C18diacid γE-γE- 17 Amide 2Aib, 3H, 5S, 19 DVSK(αMePhe)LDSK (O2Oc)- 6αMePhe, (O2Oc2-VE2- (O2Oc) 10V, C18diacid)17AARD 13αMePhe, (αMePhe)VQ(Aib)IANT- 17K, 18A, amide 20R, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 25 C18diacid γE-γE- 17 Amide 2Aib, 3H, 5S, 20 DVSK(αMePhe)LDSK (O2Oc)- 6αMePhe, (O2Oc2-VE2- (O2Oc) 10V, C18diacid)17AARD 13αMePhe, (αMePhe)VE(Aib)IANT- 17K, 18A, amide 20R, 22αMePhe, 24E, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 26 C18diacid VE 17 Amide 2Aib, 3H, 5S, 21 DVSK(αMePhe)LDSK(VE 6αMePhe, C18diacid)17AAQD 10V, (αMePhe)VESIANT-amide 13αMePhe, 17K, 18A, 22αMePhe, 24E, 25S, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 27 C20diacid γE-γE- 17 Amide 2Aib, 3H, 5S, 22 DVSK(αMePhe)LDSK (O2Oc)- 6αMePhe, (O2Oc-O2Oc-γE-γE- (O2Oc) 10V, C20diacid)17AAQD 13αMePhe, (αMePhe)VESIANT-amide 17K, 18A, 22αMePhe, 24E, 25S, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 28 C18diacid γE- 17 Amide 2Aib, 3H, 5S, 23 DVSK(αMePhe)LDSK (O2Oc)- 6αMePhe, (O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)17AAQD 13αMePhe, (αMePhe)VESIANT-amide 17K, 18A, 22αMePhe, 24E, 25S, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 29 C18diacid γE- 17 Amide 2Aib, 3H, 5S, 24 DVSK(αMePhe)LDSK (O2Oc)- 6αMePhe, (O2Oc-O2Oc-γE- (O2Oc) 10V C18diacid)17AAQD 13αMePhe, (αMePhe)VQ(Aib)IANT- 17K, 18A, amide 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 30 C20diacid γE-γE- 17 Amide 2Aib, 3H, 5S, 25 DVSK(αMePhe)LDSK (O2Oc)- 6αMePhe, (O2Oc-O2Oc-γE-γE- (O2Oc) 10V, C20diacid)17AAQD 13αMePhe, (αMePhe)VQ(Aib)IANT- 17K, 18A, amide 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)QGS(αMePhe)TS 31 C18diacid γE- 17 Amide 2Aib, 5S, 26 DVSK(αMePhe)LDSK (O2Oc)- 6αMePhe, (O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)17AAQD 13αMePhe, (αMePhe)VQWIAN-amide 17K, 18A, 22αMePhe, 26I, 27A, des29T Peptide H(Aib)QGS(αMePhe)TS 32 C18diacid γE- 17 Amide 2Aib, 5S, 27 DVSK(αMePhe)LDSK (O2Oc)- 60MePhe, (O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)17AAQD 13αMePhe, (αMePhe)VEWIAN-amide 17K, 18A, 22αMePhe, 24E, 26I, 27A, des29T Peptide H(AIb)QGTFTSDVSK 33 C18diacid γE- 17 Acid 2Aib, 10V, 28 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-yE- (O2Oc) 17K, 24R, C18diacid)17RAQDFVR 27L, 28Aib WLL(Aib)T-acid Peptide H(Aib)QGTFTSDVSK 34 C18diacid γE- 17 Acid 2Aib, 10V, 29 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-yE- (O2Oc) 17K, 20Aib, C18diacid)17RA(Aib)DF 27L, 28Aib VQWLL(Aib)T-acid Peptide H(Aib)QGTFTSDVSK 35 C18diacid γE- 17 Acid 2Aib, 10V, 30 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 24R, C18diacid)17RAQDFVR 27L, 28Aib, WLL(Aib)TG-acid 30G Peptide H(Aib)QGTFTSDVSK 36 C18diacid γE- 17 Acid 2Aib, 10V, 31 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 24R, C18diacid)17RAQDFVR 27L, 28E, WLLE(Aib)G-acid 29Aib, 30G Peptide H(Aib)QGTFTSDVSK 37 C18diacid VE 17 Amide 2Aib, 10V, 32 (αMePhe)LDSK(γE- 13αMePhe, C18diacid)17RA(Aib)DF 17K, 20Aib, VQWIANT-amide 26I, 27A Peptide H(Aib)QGTFTSDVSK 38 C18diacid γE- 17 Acid 2Aib, 10V, 33 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-yE- (O2Oc) 17K, 27E, C18diacid)17RAQDFVQ 28Aib WLE(Aib)T-acid Peptide H(Aib)QGTFTSDVSK 39 C18diacid γE- 17 Acid 2Aib, 10V, 34 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 27L, C18diacid)17RAQDFVQ 28Aib, 29E WLL(Aib)E-acid Peptide H(Aib)QGTFTSDVSK 40 C18diacid γE- 17 Acid 2Aib, 10V, 35 (αMePhe)LDTK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 16T, 17K, C18diacid)17RAQDFVQ 27L, 28Aib WLL(Aib)T-acid Peptide H(Aib)QGTFTSDVSK 41 C18diacid γE- 17 Acid 2Aib, 10V, 36 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 20R, C18diacid)17RARDFVQ 27L, 28Aib WLL(Aib)T-acid Peptide H(Aib)QGTFTSDVSK 42 C18diacid γE- 17 Acid 2Aib, 10V, 37 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 20E, C18diacid)17RAEDFVQ 27L, 28Aib WLL(Aib)T-acid Peptide H(Aib)QGTFTSDVSK 43 C18diacid γE- 17 Acid 2Aib, 10V, 38 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-yE- (O2Oc) 17K, 24E, C18diacid)17RAQDFVE 27L, 28Aib WLL(Aib)T-acid Peptide H(Aib)QGTFTSDVSK 44 C18diacid γE- 17 Acid 2Aib, 10V, 39 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 24R, C18diacid)17RAQDFVR 27L, 28Amb, WLL(Aib)TE-acid 30E Peptide H(Aib)QGTFTSDVSK 45 C18diacid γE- 17 Acid 2Aib, 10V, 40 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 27L, C18diacid)17RAQDFVQ 28Aib, WLL(Aib)T-acid Peptide H(Aib)QGTFTSDYSK 46 C18diacid γE- 17 Amide 2Aib, 41 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 27V, C18diacid)17RAQDFVQ 28(PEG)4, WLV(PEG)4-amide des29 Peptide H(Ab)QGTFTSDVSK 47 C18diacid γE- 17 Acid 2Aib, 10V, 42 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 25Aib, C18diacid)17RAQDFVQ 27V, 28A (Aib)LVAT-acid Peptide H(Aib)QGS(αMePhe)TS 114 Palmitoyl γE-γE- 17 Amide 2Aib, 5S, 43 DVSK(Dip)LDSK((PEG)4- (PEG)4 6αMePhe, γE-γE- 10V, 13Dip, Palmitoyl)17RAQD 17K, (αMePhe)VE(Aib)LEAGG- 22αMePhe, amide 24E, 25Aib, 27E, 28A, 29G, 30G Peptide H(Aib)QGS(αMePhe)TS 115 Stearoyl γE-γE- 17 Amide 2Aib, 5S, 44 DVSK(Dip)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13Dip, Stearoyl)17AAQD 17K, (αMePhe)VE(Aib)LEAGG- 22αMePhe, amide 24E, 25Aib, 27E, 28A, 29G, 30G Peptide H(Aib)QGS(αMePhe)TS 116 Stearoyl γE-γE- 17 Amide 2Aib, 5S, 45 DVSK(Dip)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13Dip, Stearoyl)17AAQD 17K, (αMePhe)VE(Aib)LANT- 22αMePhe, amide 24E, 25Aib, 27A Peptide HSQGS(αMePhe)TSDVS 117 Stearoyl γE-γE- 17 Amide 5S, 46 K(Dip)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13Dip, Stearoyl)17AAQD 17K, 18A, (αMePhe)VE(Aib)LEAGG- 22αMePhe, amide 24E, 25Aib, 27E, 28A, 29G, 30G Peptide HSQGS(αMePhe)TSDVS 118 Stearoyl γE-γE- 17 Amide 5S, 47 K(Dip)LDSK((PEG)2- (PEG)2- 6QMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13Dip, Stearoyl)17AAQD 17K, 18A, (αMePhe)VE(Aib)LANT- 22αMePhe, amide 24E, 25Aib, 27A Peptide HSQGS(αMePhe)TSDVS 119 Stearoyl γE-yE- 17 Amide 5S, 48 K(Dip)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13Dip, Stearoyl)17AAQD 17K, 18A, (αMePhe)VE(Aib)LISG- 22αMePhe, amide 24E, 25Aib, 27I, 28S, 29G Peptide HSQGS(αMePhe)TSDVS 120 Stearoyl γE-yE- 17 Amide 5S, 49 K(Dip)LDSK((PEG)2- PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13Dip, Stearoyl)17AAQD 17K, 18A, (αMePhe)VE(Aib)IANT- 22αMePhe, amide 24E, 25Aib, 26I, 27A Peptide HSQGS(αMePhe)TSDVS 121 Stearoyl γE-γE- 17 Amide 5S, 50 K(Dip)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13Dip, Stearoyl)17AAQD 17K, 18A, (αMePhe)VE(Aib)IINT- 22αMePhe, amide 24E, 25Aib, 26I, 27I Peptide HSQGS(αMePhe)TSDVS 122 Stearoyl γE-γE- 17 Amide 5S, 51 K(Dip)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13Dip, Stearoyl)17AAQD 17K, 18A, (αMePhe)VE(Aib)LLNT- 22αMePhe, amide 24E, 25Aib, 27L Peptide HSQGS(αMePhe)TSDVS 123 Stearoyl γE-γE- 17 Amide 5S, 52 K(DIp)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13Dip, Stearoyl)17AAQD 17K, 18A, (αMePhe)VE(Aib)ChaANT- 22αMePhe, amide 24E, 25Aib, 26Cha, 27A Peptide HSQGS(αMePhe)TSDVS 124 Stearoyl γE-γE- 17 Amide 5S, 53 K(Dip)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13Dip, Stearoyl)17AAQD 17K, 18A, (αMePhe)VE(Aib)VVEGG- 22αMePhe, amide 24E, 25Aib, 26V, 27V, 28E, 29G, 30G Peptide HSQGS(αMePhe)TSDVS 125 Stearoyl γE-γE- 17 Amide 5S, 54 K(Dip)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13Dip, Stearoyl)17AAQD 17K, 18A, (αMePhe)VQ(Aib)IAN- 22αMePhe, amide 25Aib, 26I, 27A, des29T Peptide HSQGS(αMePhe)TSDVS 126 Stearoyl γE-γE- 17 Amide 5S, 55 K(Dip)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13Dip, Stearoyl)17AAQD(αMePhe) 17K, 18A, VQ(Dip)LEA-amide 22αMePhe, 25Dip, 27E, 28A, des29T Peptide HSQGS(αMePhe)TSDVS 127 Stearoyl γE-γE- 17 Amide 5S, 56 K(Dip)LDSK(PEG)4-γE- (PEG)4 6αMePhe, γE- 10V, 13Dip, Stearoyl)17AAQD(αMePhe) 17K, 18A, VE(Aib)IINT-amide 22αMePhe, 24E, 25Aib, 26I, 27I Peptide HSQGS(αMePhe)TSDVS 128 Stearoyl γE-γE- 17 Amide 5S, 57 K(Dip)LDSK((PEG)8-γE- (PEG)8 6αMePhe, γE- 10V, 13Dip, Stearoyl)17AAQD(αMePhe) 17K, 18A, VE(Aib)IINT-amide 22αMePhe, 24E, 25Aib, 26I, 27I Peptide HSQGS(αMePhe)TSDVS 129 Stearoyl γE-γE- 17 Amide 5S, 58 K(Dip)LDSK((PEG)12- (PEG)12 6αMePhe, γE-γE- 10V, 13Dip, Stearoyl)17AAQD(αMePhe) 17K, 18A, VE(Aib)IINT-amide 22αMePhe, 24E, 25Aib, 26I, 27I Peptide HSQGS(αMePhe)TSDVS 130 Stearoyl (PEG)2- 17 Amide 5S, 59 K(Dip)LDSK(γE-γE- (PEG)2- 6αMePhe, (PEG)2-(PEG)2- γE-γE 10V, 13Dip, Stearoyl)17AAQD(αMePhe) 17K, 18A, VE(Aib)IINT-amide 22αMePhe, 24E, 25Aib, 26I, 27I Peptide HSQGS(αMePhe)TSDVS 131 Stearoyl (PEG)2- 17 Amide 5S, 60 K(Dip)LDSK(γE-(PEG)2- γE- 6αMePhe, γE-(PEG)2- (PEG)2- 10V, 13Dip, Stearoyl)17AAQD(αMePhe) γE 17K, 18A, VE(Aib)IINT-amide 22αMePhe, 24E, 25Aib, 26I, 27I Peptide HSQGS(αMePhe)TSDVS 132 Stearoyl γE- 17 Amide 5S, 61 K(Dip)LDSK((PEG)2-γE- (PEG)2- 6αMePhe, (PEG)2-γE- γE- 10V, 13Dip, Stearoyl)17AAQD(αMePhe) (PEG)2 17K, 18A, VE(Aib)IINT-amide 22αMePhe, 24E, 25Aib, 26I, 27I Peptide HSQGS(αMePhe)TSDVS 133 Lauryl γE-γE- 17 Amide 5S, 62 K(Dip)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13Dip, Lauryl)17AAQD(αMePhe) 17K, 18A, VE(Aib)IINT-amide 22αMePhe, 24E, 25Aib, 26I, 27I Peptide HSQGS(αMePhe)TSDVS 134 Myristoyl γE-γE- 17 Amide 5S, 63 K(Dip)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13Dip, Myristyl)17AAQD(αMePhe) 17K, 18A, VE(Aib)IINT-amide 22αMePhe, 24E, 25Aib, 26I, 27I Peptide HSQGS(αMePhe)TSDVS 135 Palmitoyl γE-γE- 17 Amide 5S, 64 K(Dip)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13Dip, Palmitoyl)17AAQD 17K, 18A, (αMePhe)VE(Aib)IINT- 22αMePhe, amide 24E, 25Aib, 26I, 27I Peptide HSQGS(αMePhe)TSDVS 136 Stearoyl γE-γE- 17 Amide 5S, 65 K(Dip)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13Dip, C18diacid)17AAQD 17K, 18A, (αMePhe)VE(Aib)IINT- 22αMePhe, amide 24E, 25Aib, 26I, 27I Peptide H(Aib)QGS(αMePhe)TS 137 Stearoyl γE-γE- 17 Amide 2Aib, 5S, 66 DVSK(Dip)LDSK(ϵ- (PEG)2- 6αMePhe, ((PEG)2-(PEG)2-γE-γE- (PEG)2 10V, 13Dip, Stearyl)17AAQD(αMeP 17K, 18A, he)VQ(Aib)IAN-amide 22αMePhe, 25Aib, 26I, 27A, des29T Peptide H(Aib)QGS(αMePhe)TS 138 Palmitoyl γE- 17 Amide 2Aib, 5S, 67 DVSK(Dip)LDSK(ϵ- (PEG)2- 6αMePhe, ((PEG)2-(PEG)2-γE- (PEG)2 10V, 13Dip, Palmitoyl)17AAQD(αMePhe) 17K, 18A, VQ(Aib)IAN- 22αMePhe, amide 25Aib, 26I, 27A, des29T Peptide H(Aib)QGTFTSDVSK 139 Palmitoyl γE- 17 Amide 2Aib, 10V, 68 (αMePhe)LDVK((PEG)4- (PEG)4 13αMePhe, γE- 16V, 17K, Palmitoyl)17RAQD 22αMePhe, (αMePhe)VE(Aib)LNleET- 24E, 25Aib, amide 27Nle, 28E Peptide H(Aib)QGTFTSDVSK 140 Stearoyl γE-γE- 17 Amide 2Aib, 10V, 69 (αMePhe)LDSK((PEG)2- (PEG)2- 13αMePhe, (PEG)2-γE-γE- (PEG)2 16V, 17K, Stearyl)17RAQD(αMePhe) 22αMePhe, VQ(Aib)LNleET- 24E, 25Aib, amide 27Nle, 28E Peptide H(Aib)QGS(αMePhe)TS 141 Stearoyl γE-γE- 17 Amide 2Aib, 5S, 70 DVSK(αMePhe)LDSK (PEG)4 6αMePhe, ((PEG)4-γE-γE- 10V, Stearoyl)17RAQD(αMePhe) 13αMePhe, VE(Aib)LEAGG- 17K, amide 22αMePhe, 24E, 25Aib, 27E, 28A, 29G, 30G Peptide H(Aib)QGS(αMePhe)TS 142 Stearoyl γE-γE- 17 Amide 2Aib, 5S, 71 DVSK(αMePhe)LDSK (PEG)4 6αMePhe, ((PEG)4-γE-γE- 10V, Stearoyl)17AAQD(αMePhe) 13αMePhe, VE(Aib)LEAGG- 17K, 18A, amide 22αMePhe, 24E, 25Aib, 27E, 28A, 29G, 30G Peptide H(Aib)QGS(αMePhe)TS 143 Palmitoyl γE-γE- 17 Amide 2Aib, 5S, 72 DVSK(αMePhe)LDSK (PEG)4 6αMePhe, ((PEG)4-γE-γE- 10V, Palmitoyl)17AAQD 13αMePhe, (αMePhe)VE(Aib)LEAGG- 17K, 18A, amide 22αMePhe, 24E, 25Aib 27E, 28A, 29G, 30G Peptide H(Aib)QGS(αMePhe)TS 144 Palmitoyl γE-γE- 17 Amide 2Aib, 5S, 73 DVSK(αMePhe)LDSK (PEG)2- 6αMePhe, ((PEG)2-(PEG)2-γE-γE- (PEG)2 10V, Palmitoyl)17AAQD 13αMePhe, (αMePhe)VQ(Aib)IAN- 17K, 18A, amide 22αMePhe, 25Aib, 26I, 27A, des29T Peptide H(Aib)QGS(αMePhe)TS 145 Stearoyl γE-γE- 17 Amide 2Aib, 5S, 74 DVSK(αMePhe)LDSK (PEG)2- 6αMePhe, ((PEG)2-(PEG)2-γE-γE- (PEG)2 10V, Stearoyl)17(B- 13αMePhe, dimethylGln)AQD 17K, 18β- (αMePhe)VE(Aib)LEAGG- dimethyl-R, amide 22αMePhe, 24E, 25Aib, 27E, 28Å, 29G, 30G Peptide H(Aib)QGS(αMePhe)TS 146 Palmitoyl γE-γE- 17 Amide 2Aib, 5S, 75 DVSK(αMePhe)LDSK (PEG)2- 6αMePhe, ((PEG)2-(PEG)2-γE-γE- (PEG)2 10V, Palmitoyl)17AAQDIVQII 13αMePhe, AN-amide 17K, 18A, 22I, 25I, 26I, 27A, des29T Peptide H(Aib)QGS(αMePhe)TS 147 Stearoyl γE-γE- 17 Amide 2Aib, 5S, 76 DVSK(αMePhe)LDSK (PEG)2- 6αMePhe, ((PEG)2-(PEG)2-γE-γE- (PEG)2 10V, Stearoyl)17AAQD 13αMePhe, (αMePhe)VQ(Aib)VVEGG- 17K, 18A, amide 22αMePhe, 25Aib, 26V, 27V, 28E, 29G, 30G Peptide H(Aib)QGS(αMePhe)TS 148 Stearoyl γE-γE- 17 Amide 2Aib, 5S, 77 DVSK(αMePhe)LDSK (PEG)2- 6αMePhe, ((PEG)2-(PEG)2-γE-γE- (PEG)2 10V, Stearoyl)17AAQD 13αMePhe, (αMePhe)VQ(Aib)LISG- 17K, 18A, amide 22αMePhe, 25Aib, 27I, 28S, 29G Peptide HSQGS(αMePhe)TSDVS 149 Stearoyl γE-γE- 17 Amide 5S, 78 K(αMePhe)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, Stearoyl)17AAQD 13αMePhe, (αMePhe)VQ(Aib)LEAGG- 17K, 18A, amide 22αMePhe, 25Aib, 27E, 28A, 29G, 30G Peptide HSQGS(αMePhe)TSDVS 150 Palmitoyl yE-yE- 17 Amide 5S, 79 K(αMePhe)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, Palmitoyl)17AAQD 13αMePhe, (αMePhe)VQ(Aib)LEAGG- 17K, 18A, amide 22QMePhe, 25Aib, 27E, 28A, 29G, 30G Peptide HSQGS(αMePhe)TSDVS 151 Palmitoyl yE-yE- 17 Amide 5S, 80 K(αMePhe)LDSK(PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, Margaroyl)17AAQD 13αMePhe, (αMePhe)VQ(Aib)LEAGG- 17K, 18A, amide 22αMePhe, 25Aib, 27E, 28A, 29G, 30G Peptide HSQGS(αMePhe)TSDVS 152 Stearoyl γE-γE- 17 Amide 5S, 81 K(αMePhe)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, Stearoyl)17AAQD 13αMePhe, (αMePhe)VE(Aib)LEAGG- 17K, 18A, amide 22αMePhe, 25Aib, 27E, 28A, 29G, 30G Peptide HSQGS(αMePhe)TSDVS 153 Stearoyl γE-γE- 17 Amide 5S, 82 K(αMePhe)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, Stearoyl)17AAQD 13αMePhe, (αMePhe)VQ(Aib)IANT- 17K, 18A, amide 22αMePhe, 25Aib, 26I, 27A Peptide HSQGS(αMePhe)TSDVS 154 Stearoyl γE-γE- F 17 Amide 5S, 83 K(αMePhe)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, Stearoyl)17AAQD(αMePhe) 13αMePhe, VQ(Aib)IINT-amide 17K, 18A, 22αMePhe, 25Aib, 26I, 27I Peptide HSQGS(αMePhe)TSDVS 155 Stearoyl γE-γE- 17 Amide 5S, 84 K(αMePhe)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, Stearoyl)17AAQD 13αMePhe, (αMePhe)VQ(Aib)LLNT- 17K, 18A, amide 22αMePhe, 25Aib, 27L Peptide HSQGS(αMePhe)TSDVS 156 Stearoyl γE-γE- 17 Amide 5S, 85 K(αMePhe)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, Stearoyl)17AAQD 13αMePhe, (αMePhe)VQ(Aib)VVEGG- 17K, 18A, amide 22αMePhe, 25Aib, 26V, 27V, 28E, 29G, 30G Peptide HSQGS(αMePhe)TSDVS 157 Stearoyl γE-γE- 17 Amide 5S, 86 K(αMePhe)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, Stearoyl)17AAQD(αMePhe) 13αMePhe, VQ(Aib)IAN-amide 17K, 18A, 22αMePhe, 25Aib, 26I, 27A, des29T Peptide HSQGS(αMePhe)TSDVS 158 Palmitoyl γE-γE- 17 Amide 5S, 87 K(αMePhe)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, Palmitoyl)17AAQD 13αMePhe, (αMePhe)VQ(Aib)IAN- 17K, 18A, amide 22αMePhe, 25Aib, 26I, 27A, des29T Peptide HSQGS(αMePhe)TSDVS 159 Margaroyl yE-yE- 17 Amide 5S, 88 K(αMePhe)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, Margaroyl)17AAQD 13αMePhe, (αMePhe)VQ(Aib)IAN- 17K, 18A, amide 22αMePhe, 25Aib, 26I, 27A, des29T Peptide HSQGS(αMePhe)TSDVS 160 Palmitoyl γE-γE- 17 Amide 5S, 89 K(αMePhe)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, Palmitoyl)17AAQD 13αMePhe, (αMePhe)VQIIAN-amide 17K, 18A, 22αMePhe, 25Aib, 26I, 27A, des29T Peptide HSQGS(αMePhe)TSDVS 161 Palmitoyl γE-yE- 17 Amide 5S, 90 K(αMePhe)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, Palmitoyl)17AAQD 13αMePhe, (αMePhe)VE(Aib)IAN- 17K, 18A, amide 22αMePhe, 24E, 25Aib, 26I, 27A, des29T Peptide HSQGS(αMePhe)TSDVS 162 Palmitoyl γE-γE- 17 Amide 5S, 91 K(αMePhe)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, Palmitoyl)17AAQD 13αMePhe, (αMePhe)VQ(Aib)IAG- 17K, 18A, amide 22αMePhe, 25Aib, 26I, 27A, 28A, des29T Peptide HSQGS(αMePhe)TSDVS 163 Stearoyl γE-γE- 17 Amide 5S, 92 K(AIb)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13Aib, Stearoyl)17AAQD(αMePhe) 17K, 18A, VQ(Aib)LEA-amide 22αMePhe, 25Aib, 27E, 28A, des29T Peptide HSQGS(αMePhe)TSDVS 164 Stearoyl γE-γE- 17 Amide 5S, 93 K(AIb)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13Aib, Stearoyl)17AAQD(αMePhe) 17K, 18A, VQ(Aib)LAN-amide 22αMePhe, 25Aib, 27A, des29T Peptide HSQGS(αMePhe)TSDVS 165 Stearoyl γE-γE- 17 Amide 5S, 94 K(Aib)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13Aib, Stearoyl)17AAQD(αMePhe) 17K, 18A, VQ(Aib)LSE-amide 22αMePhe, 25Aib, 27S, 28E, des29T Peptide HSQGS(αMePhe)TSDVS 166 Stearoyl γE-γE- 17 Amide 5S, 95 K(AIb)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13Aib, Stearoyl)17AAQD 17K, 18A, Phe)VQ(Aib)LANT- 22αMePhe, (αMeamide 25Aib, 27Å Peptide HSQGS(αMePhe)TSDVS 167 Stearoyl γE-γE- 17 Amide 5S, 96 K(Aib)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13Aib, Stearoyl)17AAQD 17K, 18A, (αMePhe)VQ(Aib)LEAGG- 22αMePhe, amide 25Aib, 27E, 28A, 29G, 30G Peptide HSQGS(αMePhe)TSDVS 168 Stearoyl γE-γE- 17 Amide 5S, 97 K(AIb)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13Aib, Stearoyl)17AAQD(αMePhe) 17K, 18A, VQ(Aib)IAN-amide 22αMePhe, 25Aib, 26I, 27A, des29T Peptide HSQGS(αMePhe)TSDVS 169 Stearoyl γE-γE- 17 Amide 5S, 98 K(AIb)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13Aib, Stearoyl)17AAQD(αMePhe) 17K, 18A, VQ(Aib)IIE-amide 22αMePhe, 25Aib, 26I, 27I, 28E, des29T Peptide HSQGS(αMePhe)TSDVS 170 Palmitoyl γE-γE- 17 Amide 5S, 99 K(Aib)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13Aib, Palmitoyl)17AAQD 17K, 18A, (αMePhe)VQ(Aib)IAN- 22αMePhe, amide 25Aib, 26I, 27A, des29T Peptide H(Aib)QGS(αMePhe)TS 171 Stearoyl γE-γE- 17 Amide 2Aib, 5S, 100 DVSK(Aib)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13Aib, Stearyl)17AAQD(αMePhe) 17K, 18A, VQ(Aib)IAN-amide 22αMePhe, 25Aib, 26I, 27A, des29T Peptide H(Aib)QGS(αMePhe)TS 172 Stearoyl γE-γE- 17 Amide 2Aib, 5S, 101 DVSK(AIb)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13Aib, Stearyl)17AAQD(αMePhe) 17K, 18A, VQ(Aib)IAN-acid 22αMePhe, 25Aib, 26I, 27A, des29T Peptide H(Aib)QGS(αMePhe)TS 173 Stearoyl γE-γE- 17 Amide 2Aib, 5S, 102 DVSK(Aib)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13Aib, Stearyl)17RAQD(αMePhe) 17K, 18R, VQ(Aib)IAN-amide 22αMePhe, 25Aib, 26I, 27A, des29T Peptide H(Aib)QGS(αMePhe)TS 174 Stearoyl γE-γE- 17 Amide 2Aib, 5S, 103 DVSK(Aib)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13Aib, Stearyl)17AAQD(αMePhe) 17K, 18A, VQWIAN-amide 22αMePhe, 26I, 27A, des29T Peptide HTQGS(αMePhe)TSDVS 175 Stearoyl γE-γE- 17 Amide 2T,5S, 104 K(Aib)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13Aib, Stearyl)17AAQD(αMePhe) 17K, 18A, VQ(Aib)IAN-amide 22αMePhe, 25Aib, 26I, 27A, des29T Peptide HSQGS(αMePhe)TSDVS 176 Palmitoyl γE-γE- 17 Amide 5S, 105 K(AIb)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13Aib, Palmitoyl)17QAQD(αMePhe) 17K, 18Q, VQ(Aib)IAN- 22αMePhe, amide 25Aib, 26I, 27A, des29T Peptide HSQGS(αMePhe)TSDVS 177 Palmitoyl γE-γE- 17 Amide 5S, 106 K(Aib)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13Aib, Palmitoyl)17AAQD(αMePhe) 17K, 18A, VQHIAN-amide 22αMePhe, 25H, 26I, 27A, des29T Peptide HSQGS(αMePhe)TSDVS 178 Palmitoyl γE-γE- 17 Amide 5S, 107 K(Aib)LDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13Aib, Palmitoyl)17QAQD(αMePhe) 17K, 18Q, VQHIAN-amide 22αMePhe 25H, 26I, 27A, des29T Peptide HSQGS(αMePhe)TSDVS 179 C18diacid γE- 17 Amide 5S, 108 K(AIb)LDSK(O2Oc- (O2Oc)- 6αMePhe, O2Oc-γE- (O2Oc) 10V, 13Aib, C18diacid)17AAQD(αMePhe) 17K, 18A, VQ(Aib)IAN- 22αMePhe, amide 25Aib, 26I, 27A, des29T Peptide HSQGS(αMePhe)TSDVS 180 C18diacid γE- 17 Amide 5S, 109 (Ac- (O2Oc)- 6αMePhe, Lys)(Aib)LDSK(O2Oc- (O2Oc) 10V, 12Ac- O2Oc-yE- Lys, 13Aib, C18diacid)17AAQD(αMePhe) 17K, 18A, VQ(Aib)IAN- 22αMePhe, amide 25Aib, 26I, 27A, des29T Peptide HSQGS(αMePhe)TSDVS 181 Stearoyl γE-γE- 17 Amide 5S, 110 (Ac- (PEG)2- 6αMePhe, Lys)(Aib)LDSK((PEG)2- (PEG)2 10V, 12Ac- (PEG)2-γE-γE- Lys, 13Aib, Stearyl)17AAQD(αMePhe) 17K, 18A, VQ(Aib)IAN-amide 22αMePhe, 25Aib, 26I, 27A, des29T Peptide HSQGS(αMePhe)TSDVS 182 Palmitoyl γE-γE- 17 Amide 5S, 111 KILDSK((PEG)2-(PEG)2- (PEG)2- 6αMePhe, γE-γE- (PEG)2 10V, 13I, Palmitoyl)17AAQD(αMePhe) 17K, 18A, VQ(Aib)IAN- 22αMePhe, amide 25Aib, 26I, 27A, des29T Peptide HSQGS(αMePhe)TSDVS 183 Palmitoyl γE-γE- 17 Amide 5S, 112 KILDSK((PEG)2-(PEG)2- (PEG)2- 6αMePhe, γE-γE- (PEG)2 10V, 13I, Palmitoyl)17AAQD(αMePhe) 17K, 18A, VQIIAN-amide 22αMePhe, 25I, 26I, 27A, des29T Peptide HSQGS(αMePhe)TSDVS 184 Palmitoyl γE-γE- 17 Amide 5S, 113 KILDSK((PEG)2-(PEG)2- (PEG)2- 6αMePhe, γE-γE- (PEG)2 10V, 13I, Palmitoyl)17AAQD(αMePhe) 17K, 18A, VQIIAG-amide 22αMePhe, 25I, 26I, 27A, 28G, des29T Peptide HSQGS(αMePhe)TSDVS 185 Palmitoyl γE-γE- 17 Amide 5S, 114 KILDSK((PEG)2-(PEG)2- (PEG)2- 6αMePhe, γE-γE- (PEG)2 10V, 13I, Palmitoyl)17AAQD(αMePhe) 17K, 18A, VEIIAN-amide 22αMePhe, 24E, 25I, 26I, 27A, des29T Peptide HSQGS(αMePhe)TSDVS 186 Palmitoyl γE-γE- 17 Amide 5S, 115 KILDSK((PEG)2-(PEG)2- (PEG)2- 6αMePhe, γE-γE- (PEG)2 10V, 13I, Palmitoyl)17AAQD(αMePhe) 17K, 18A, VQ(αMePhe)IAN- 22αMePhe, amide 25αMePhe, 26I, 27A, des29T Peptide HSQGS(αMePhe)TSDVS 187 Palmitoyl γE-γE- 17 Amide 5S, 116 KILDSK((PEG)2-(PEG)2- (PEG)2- 6αMePhe, γE-γE- (PEG)2 10V, 13I, Palmitoyl)17AAQD(αMePhe) 17K, 18A, VEWIINT-amide 22αMePhe, 24E, 26I, 27I Peptide HSQGS(αMePhe)TSDVS 188 Stearoyl γE-γE- 17 Amide 5S, 117 KILDSK((PEG)2-(PEG)2- (PEG)2- 6αMePhe, γE-γE- (PEG)2 10V, 13I, Stearoyl)17AAQD(αMePhe) 17K, 18A, VQ(Aib)IINT-amide 22αMePhe, 25Aib, 26I, 27I Peptide HSQGS(αMePhe)TSDVS 189 Palmitoyl γE-γE- 17 Amide 5S, 118 KILDSK((PEG)2-(PEG)2- (PEG)2- 6αMePhe, γE-γE- (PEG)2 10V, 13I, Palmitoyl)17AAQD(αMePhe) 17K, 18A, VQ(Aib)IINT- 22αMePhe, amide 25Aib, 26I, 27I Peptide HSQGS(αMePhe)TSDVS 190 Myristovi γE-γE- 17 Amide 5S, 119 KILDSK((PEG)2-(PEG)2- (PEG)2- 6αMePhe, γE-γE- (PEG)2 10V, 13I, Myristoyl)17AAQD(αMePhe) 17K, 18A, VQ(Aib)IINT- 22αMePhe, amide 25Aib, 26I, 27I Peptide HSQGS(αMePhe)TSDVS 191 Stearoyl γE- 17 Amide 5S, 120 KILDSK((PEG)2-(PEG)2- (PEG)2- 60MePhe, γE- (PEG)2 10V, 13I, Stearoyl)17AAQD(αMePhe) 17K, 18A, VQ(Aib)IINT-amide 22αMePhe, 25Aib, 26I, 27I Peptide HSQGS(αMePhe)TSDVS 192 Palmitoyl γE- 17 Amide 5S, 121 KILDSK((PEG)2-(PEG)2- (PEG)2- 6αMePhe, γE- (PEG)2 10V, 13I, Palmitoyl)17AAQD(αMePhe) 17K, 18A, VQ(Aib)IINT- 22αMePhe, amide 25Aib, 26I, 27I Peptide HSQGS(αMePhe)TSDVS 193 Myristoyl γE- 17 Amide 5S, 122 KILDSK((PEG)2-(PEG)2- (PEG)2- 6αMePhe, γE- (PEG)2 10V, 13I, Myristoyl)17AAQD(αMePhe) 17K, 18A, VQ(Aib)IINT- 22αMePhe, amide 25Aib, 26I, 27I Peptide H(Aib)QGS(αMePhe)TS 194 Palmitoyl γE-γE- 17 Amide 2Aib, 5S, 123 DVSKILDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13I, Palmitoyl)17AAQD(αMePhe) 17K, 18A, VQIIAN-amide 22αMePhe, 25I, 26I, 27A, des29T Peptide H(Aib)QGS(αMePhe)TS 195 Stearoyl γE-γE- 17 Amide 2Aib, 5S, 124 DVSKILDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13I, Stearoyl)17AAQD(αMePhe) 17K, 18A, VQ(Aib)IINT-amide 22αMePhe, 25Aib, 26I, 27I Peptide H(Aib)QGS(αMePhe)TS 196 Palmitoyl γE-γE- 17 Amide 2Aib, 5S, 125 DVSKILDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13I, Palmitoyl)17AAQD(αMePhe) 17K, 18A, VQ(Aib)IINT- 22αMePhe, amide 25Aib, 26I, 27I Peptide H(Aib)QGS(αMePhe)TS 197 Myristoyl γE-γE- 17 Amide 2Aib, 5S, 126 DVSKILDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE-γE- (PEG)2 10V, 13I, Myristoyl)17AAQD(αMePhe) 17K, 18A, VQ(Aib)IINT- 22αMePhe, amide 25Aib, 26I, 27I Peptide H(Aib)QGS(αMePhe)TS 198 Stearoyl γE- 17 Amide 2Aib, 5S, 127 DVSKILDSK((PEG)2- (PEG)2- 6oMePhe, (PEG)2-yE- (PEG)2 10V, 13I, Stearoyl)17AAQD(αMePhe) 17K, 18A, VQ(Aib)IINT-amide 22αMePhe, 25Aib, 26I, 27I Peptide H(Aib)QGS(αMePhe)TS 199 Palmitoyl γE- 17 Amide 2Aib, 5S, 128 DVSKILDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE- (PEG)2 10V, 13I, Palmitoyl)17AAQD(αMePhe) 17K, 18A, VQ(Aib)IINT- 22αMePhe, amide 25Aib, 26I, 27I Peptide H(Aib)QGS(αMePhe)TS 200 Myristoyl γE- 17 Amide 2Aib, 5S, 129 DVSKILDSK((PEG)2- (PEG)2- 6αMePhe, (PEG)2-γE- (PEG)2 10V, 13I, Myristoyl)17AAQD(αMePhe) 17K, 18A, VQ(Aib)IINT- 22αMePhe, amide 25Aib, 26I, 27I Peptide H(αMeSer)QGS(αMePhe) 201 Stearoyl γE-γE- 17 Amide 2αMeSer, 130 TSDVSKILDSK((PEG)2- (PEG)2- 5S, (PEG)2-γE-γE- (PEG)2 6αMePhe, Stearoyl)17AAQD(αMePhe) 10V, 13I, VQ(Aib)IINT-amide 17K, 18A, 22αMePhe, 25Aib, 26I, 27I Peptide H(αMeSer)QGS(αMePhe) 202 Palmitoyl γE-γE- 17 Amide 2oMeSer, 131 TSDVSKILDSK((PEG)2- (PEG)2- 5S, (PEG)2-γE-γE- (PEG)2 6αMePhe, Palmitoyl)17AAQD(αMePhe) 10V, 13I, VQ(Aib)IINT- 17K, 18A, amide 22αMePhe, 25Aib, 26I, 27I Peptide H(αMeSer)QGS(αMePhe) 203 Myristoyl γE-γE- 17 Amide 2αMeSer, 132 TSDVSKILDSK((PEG)2- (PEG)2- 5S, (PEG)2-γE-yE- (PEG)2 6αMePhe Myristoyl)17AAQD(αMePhe) 10V, 13I, VQ(Aib)IINT- 17K, 18A, amide 22αMePhe, 25Aib, 26I, 27I Peptide H(αMeSer)QGS(αMePhe) 204 Stearoyl γE- 17 Amide 2αMeSer, 133 TSDVSKILDSK((PEG)2- (PEG)2- 5S, (PEG)2-γE- (PEG)2 6αMePhe, Stearoyl)17AAQD(αMePhe) 10V, 13I, VQ(Aib)IINT-amide 17K, 18A, 22αMePhe, 25Aib, 26I, 27I Peptide H(αMeSer)QGS(αMePhe) 205 Palmitoyl γE- 17 Amide 2αMeSer, 134 TSDVSKILDSK((PEG)2- (PEG)2- 5S, (PEG)2-γE- (PEG)2 6αMePhe, Palmitoyl)17AAQD(αMePhe) 10V, 13I, VQ(Aib)IINT- 17K, 18A, amide 22αMePhe, 25Aib, 26I, 27I Peptide H(αMeSer)QGS(αMePhe) 206 Myristoyl γE- 17 Amide 2αMeSer, 135 TSDVSKILDSK((PEG)2- (PEG)2- 5S, (PEG)2-γE- (PEG)2 6αMePhe, Myristoyl)17AAQD(αMePhe) 10V, 13I, VQ(Aib)IINT- 17K, 18A, amide 22αMePhe, 25Aib, 26I, 27I Peptide H(Aib)QGTFTSDVSK 48 C18diacid γE 17 Acid 2Aib, 10V, 136 (αMePhe)LDSK(yE-yE- γE(O2Oc)- 13αMePhe, O2Oc-O2Oc-γE-γE- (O2Oc)- 17K, 20R, C18diacid)17RARDFVR γE-γE 24R, 27L, WLLE(Aib)G-acid 28E, 29Aib, 30G Peptide H(Aib)QGTFTSDVSK 49 C18diacid γE- 17 Acid 2Aib, 10V, 137 (αMePhe)LDSK(yE-yE- γE(O2Oc)- 13αMePhe, O2Oc-O2Oc-γE-γE- (O2Oc)- 17K, 24R, C18diacid)17RAQDFVR γE-γE 27L, 28E, WLLEG(Aib)-acid 29G, 30Aib Peptide H(Aib)QGTFTSDVSK 50 C18diacid γE- 17 Acid 2Aib, 10V, 138 (αMePhe)LDSK(yE-yE- γE(O2Oc)- 13αMePhe, O2Oc-O2Oc-γE-γE- (O2Oc)- 17K, 24R, C18diacid)17RAQDFVR γE-γE 27L, 28E, WLLE(Alb)G-acid 29Aib, 30G Peptide H(Aib)QGTFTSDVSK 51 C20diacid γE- 17 Acid 2Aib, 10V, 139 (αMePhe)LDSK(γE-γE- γE(O2Oc)- 13αMePhe, O2Oc-O2Oc-γE-γE- (O2Oc)- 17K, 24R, C20diacid)17RAQDFVR γE-γE 27L, 28E, WLLE(Aib)G-acid 29Alb, 30G Peptide H(Aib)QGTFTSDVSK 52 C18diacid γE- 17 Acid 2Aib, 10V, 140 (αMePhe)LDTK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 16T, 17K, C18diacid)17RAQDFVR 24R, 27L, WLLE(Aib)G-acid 28E, 29Aib, 30G Peptide H(Aib)QGTFTSDVSK 53 C18diacid γE- 17 Acid 2Aib, 10V, 141 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O(αM2Oc-γE- (O2Oc) 17K, 24A, C18diacid)17RAQDFVA 27L, 28E, WLLE(Aib)G-acid 29Aib, 30G Peptide H(Aib)QGTFTSDVSK 54 C18diacid γE- 17 Acid 2Aib, 10V, 142 (αMePhe)LDSK(O2OC- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 20R, C18diacid)17RARDFVA 24A, 27L, WLLE(Aib)G-acid 28E, 29Aib, 30G Peptide H(Aib)QGTFTSDVSK 55 C18diacid γE- 17 Acid 2Aib, 10V, 143 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 20R, C18diacid)17RARDFVQ 27L, 28E, WLLE(Aib)G-acid 29Aib, 30G Peptide H(Aib)QGTFTSDVSK 56 C18diacid γE- 17 Acid 2Aib, 10V, 144 (αMePhe)LDSK(yE-yE- γE(O2Oc)- 13αMePhe, O2Oc-O2Oc-γE-γE- (O2Oc)- 17K, 20R, C18diacid)17RARDFVR γE-γE 24R, 27L, WLLE(Aib)G-acid 28E, 29Aib, 30G Peptide H(Aib)QGTFTSDVSK 57 C18diacid γE- 17 Acid 2Aib, 10V, 145 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 24R, C18diacid)17RAQDFVR 27A, 28S, WLASRGI-acid 29R, 30G, 31| Peptide H(Aib)QGTFTSDVSK 58 C18diacid γE- 17 Acid 2Aib, 10V, 146 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 24R, C18diacid)17RAQDFVR 27A, 28S, WLASR-acid 29R Peptide H(Aib)QGTFTSDVSK 59 C18diacid γE- 17 Acid 2Aib, 10V, 147 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 24R, C18diacid)17RAQDFVR 27E, 28A, WLEA(Aib)G-acid 29Aib, 30G Peptide H(Aib)QGTFTSDVSK 60 C18diacid γE- 17 Acid 2Aib, 10V, 148 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 24R, C18diacid)17RAQDFVR 26I, 27A, WIAE(Aib)G-acid 28E, 29Aib, 30G Peptide H(Aib)QGTFTSDVSK 61 C18diacid γE- 17 Acid 2Aib, 10V, 149 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 24R, C18diacid)17RAQDFVR 26V, 27V, WVVE(Aib)G-acid 28E, 29Aib, 30G Peptide H(Aib)QGTFTSDVSK 62 C18diacid γE- 17 Acid 2Aib, 10V, 150 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 27L, C18diacid)17RAQDFVQ 28Aib, 30E WLL(Aib)TE-acid Peptide H(Aib)OGTFTSDVSK 63 C20diacid γE- 17 Acid 2Aib, 10V, 151 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 24R, C20diacid)17RAQDFVR 27L, 28Aib, WLL(Aib)TE-acid 30E Peptide H(Aib)QGTFTSDVSK 64 C18diacid γE- 17 Acid 2Aib, 10V, 152 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 24R, C18diacid)17RAQDFVR 27L, 28Aib, WLL(Ab)E-acid 29E Peptide H(Aib)QGTFTSDVSK 65 C20diacid γE- 17 Acid 2Aib, 10V, 153 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 24R, C20diacid)17RAQDFVR 27L, 28Aib, WLL(Aib)E-acid 29E Peptide H(Aib)QGTFTSDVSK 65 C18diacid γE 17 Acid 2Aib, 10V, 154 (αMePhe)LDSK(γE- 13αMePhe, C18diacid)17RAQDFVQ 17K, 27L, WLL(Aib)T-acid 28Aib Peptide H(Aib)QGTFTSDVSK 66 C18diacid γE 17 Acid 2Aib, 10V, 155 (αMePhe)LDSK(γE- 13αMePhe, C18diacid)17RAQDFVR 17K, 24R, WLLE(Aib)G-acid 27L, 28E, 29Aib, 30G Peptide H(Aib)QGTFTSDVSK 67 C18diacid γE- 17 Acid 2Aib, 10V, 156 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 24R, C18diacid)17RAQDFVR 27L, 28E, WLLEG(Aib)-acid 29G, 30Aib Peptide H(Aib)QGTFTSDVSK 68 C18diacid γE 17 Acid 2Aib, 10V, 157 (αMePhe)LDSK(γE- 13αMePhe, C18diacid)17RAQDFVR 17K, 24R, WLLEG(Aib)-acid 27L, 28E, 29G, 30Aib Peptide H(Aib)QGTFTSDVSK 69 C20diacid γE- 17 Acid 2Aib, 10V, 158 (αMePhe)LDSK(O2OC- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 24R, C20diacid)17RAQDFVR 27L, 28E, WLLE(Aib)G-acid 29Aib, 30G Peptide H(Aib)QGTFTSDVSK 70 C20diacid γE- 17 Acid 2Aib, 10V, 159 (αMePhe)LDTK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 16T, 17K, C20diacid)17RAQDFVR 24R, 27L, WLLE(Aib)G-acid 28E, 29Aib, 30G Peptide H(Aib)QGTFTSDVSK 71 C18diacid γE- 17 Acid 2Aib, 10V, 160 (αMePhe)LESK(O2Oc-O2Oc- (O2Oc)- 13αMePhe, γE- (O2Oc) 15E, 17K, C18diacid)17RAQDFVR 24R, 27L, WLLE(Aib)G-acid 28E, 29Aib, 30G Peptide H(Aib)QGTFTSDVSK 72 C18diacid γE- 17 Acid 2Aib, 10V, 161 (αMePhe)LEAK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 15E, 16A, C18diacid)17RARDFVA 17K, 20R, WLLE(Aib)G-acid 24A, 27L, 28E, 29Aib, 30G Peptide H(Aib)QGTFTSDVSK 73 C18diacid γE- 17 Acid 2Aib, 10V, 162 (αMePhe)LDSK(O2OC- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 24R, C18diacid)17RAQDFVR 26I, 27A, WIA(Aib)TE-acid 28Aib, 30E Peptide H(Aib)QGTFTSDVSK 74 C18diacid γE- 17 Acid 2Aib, 10V, 163 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 24R, C18diacid)17RAQDFVR 27L, 28E, WLLE(Aib)A-acid 29Aib, 30A Peptide H(Aib)QGTFTSDVSK 75 C18diacid γE- 17 Acid 2Aib, 10V, 164 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 24R, C18diacid)17RAQDFVR 27L, 28E, WLLEA(Aib)-acid 29A, 30Aib Peptide H(Aib)QGTFTSDVSK 76 C18diacid γE- 17 Acid 2Aib, 10V, 165 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 24R, C18diacid)17RAQDFVR 27V, 28Aib, WLV(Aib)TE-acid 30E Peptide H(Aib)QGTFTSDVSK 77 C18diacid γE- 17 Acid 2Aib, 10V, 166 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 20R, C18diacid)17RARDFVR 24R, 27L, WLL(Aib)TE-acid 28Aib, 30E Peptide H(Aib)QGTFTSDVSK 78 C18diacid γE- 17 Acid 2Aib, 10V, 167 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 20R, C18diacid)17RARDFVA 24A, 27L, WLL(Aib)TE-acid 28Aib, 30E Peptide H(Aib)QGTFTSDVSK 79 C18diacid γE- 17 Acid 2Aib, 10V, 168 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 20L, C18diacid)17RALDFVR 24A, 27L, WLL(Aib)TE-acid 28Aib, 30E Peptide H(Aib)QGTFTSDVSK 80 C18diacid γE- 17 Acid 2Aib, 10V, 169 (αMePhe)LELK(O2Oc-O2Oc- (O2Oc)- 13αMePhe, γE- (O2Oc) 15E, 16L, C18diacid)17RAQDFVR 17K, 24R, WLL(Aib)TE-acid 27L, 28Aib, 30E Peptide H(Aib)QGTFTSDVSK 81 C18diacid γE- 17 Acid 2Aib, 10V, 170 (αMePhe)LDEK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 16E, 17K, C18diacid)17RAQDFVR 24R, 27L, WLL(Aib)TE-acid 28Aib, 30E Peptide H(Ab)QGTFTSDVSK 82 C18diacid γE- 17 Acid 2Aib, 10V, 171 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 24R, C18diacid)17RAQDFVR 27E, 28Aib, WLE(Aib)TE-acid 30E Peptide H(Aib)QGTFTSDVSK 83 C18diacid γE- 17 Acid 2Aib, 10V, 172 (αMePhe)LESK(O2Oc-O2Oc- (O2Oc)- 13αMePhe, γE- (O2Oc) 15E, 17K, C18diacid)17RAQDFVR 24R, 27L, WLL(Aib)TE-acid 28Aib, 30E Peptide H(Aib)QGTFTSDVSK 84 C18diacid γE- 17 Acid 2Aib, 10V, 173 (αMePhe)LESK(O2Oc-O2Oc- (O2Oc)- 13αMePhe, γE- (O2Oc) 15E, 17K, C18diacid)17RAQDFVR 24R, 27L, WLL(Aib)E-acid 28Alb, 29E Peptide H(Aib)QGTFTSDVSK 85 C18diacid γE- 17 Acid 2Aib, 10V, 174 (αMePhe)LDTK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 16T, 17K, C18diacid)17RAQDFVR 24R, 27L, WLL(Aib)TE-acid 28Aib, 30E Peptide H(Ab)QGTFTSDVSK 86 C18diacid γE- 17 Acid 2Aib, 10V, 175 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 24R, C18diacid)17RAQDFVR 27A, 28Aib, WLA(Aib)TE-acid 30E Peptide H(Aib)QGTFTSDVSK 87 C18diacid γE- 17 Acid 2Aib, 10V, 176 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-yE- (O2Oc) 17K, 24R, C18diacid)17RAQDFVR 27A, 28Aib, WLL(Aib)TA-acid 30A Peptide H(Aib)QGTFTSDVSK 88 C18diacid γE- 17 Acid 2Aib, 10V, 177 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 24R, C18diacid)17RAQDFVR 27A, 28Aib, WLL(Aib)TK-acid 30K Peptide H(Aib)QGTFTSDVSK 89 C18diacid γE- 17 Acid 2Aib, 10V, 178 (αMePhe)LDKK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 16K, 17K, C18diacid)17RAQDFVR 24R, 27L, WLL(Aib)TE-acid 28Aib, 30E Peptide H(Aib)QGTFTSDVSK 90 C18diacid γE- 17 Acid 2Aib, 10V, 179 (αMePhe)LDSK(O2OC- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 24R, C18diacid)17RAQDFVR 27L, 28E, WLLEAG-acid 29A, 30G Peptide H(Aib)QGTFTSDVSK 91 C18diacid γE- 17 Acid 2Aib, 10V, 180 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-yE- (O2Oc) 17K, 24R, C18diacid)17RAQDFVR 27L, 28A, WLLA(Aib)G-acid 29Aib, 30G Peptide H(Aib)QGTFTSDVSK 92 C18diacid (O2Oc)- 17 Acid 2Aib, 10V, 181 (αMePhe)LDSK(O2Oc- (O2Oc) 13αMePhe, O2Oc- 17K, 24R, C18diacid)17RAQDFVR 27L, 28E, WLLE(Aib)G-acid 29Aib, 30G Peptide H(Aib)QGTFTSDVSK 93 C18diacid γE- 17 Acid 2Aib, 10V, 182 (αMePhe)LDKK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 16K, 17K, C18diacid)17RAQDFVR 24R, 27L, WLLE(Aib)G-acid 28E, 29Alb, 30G Peptide H(Aib)QGTFTSDVSK 94 C18diacid γE- 17 Acid 2Aib, 10V, 183 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 24R, C18diacid)17RAQDFVR 27L, 28E, WLLE(Aib)K-acid 29Aib, 30K Peptide H(Aib)QGTFTSDVSK 95 C18diacid (O2Oc)- 17 Acid 2Aib, 10V, 184 (αMePhe)LDKK(O2Oc- (O2Oc) 13αMePhe, O2Oc- 16K, 17K, C18diacid)17RAQDFVR 24R, 27L, WLLA(Aib)K-acid 28A, 29Aib, 30K Peptide H(Aib)QGTFTSDVSK 96 C18diacid γE- 17 Amide 2Aib, 10V, 185 (αMePhe)LDTK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 16T, 17K, C18diacid)17RAQDFVR 24R, 27L, WLLE(Aib)G-amide 28E, 29Aib, 30G Peptide H(Aib)QGTFTSDVSK 97 C18diacid γE- 17 Acid 2Aib, 10V, 186 (αMePhe)LDTK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 16T, 17K, C18diacid)17RAQDFVR 24R, 27L, WLLEAG-acid 28E, 29A, 30G Peptide H(Aib)QGTFTSDVSK 98 C18diacid γE- 17 Acid 2Aib, 10V, 187 (αMePhe)LDTK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 16T, 17K, C18diacid)17RARDFVR 20R, 24R, WLVE(Aib)G-acid 27V, 28E, 29Aib, 30G Peptide H(Aib)QGTFTSDVSK 99 C18diacid γE- 17 Acid 2Aib, 10V, 188 (αMePhe)LDTK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 16T, 17K, C18diacid)17RARDFVQ 20R, 27L, WLLE(Aib)G-acid 28E, 29Aib, 30G Peptide H(Aib)QGTFTSDVSK 100 C18diacid γE- 17 Acid 2Aib, 10V, 189 (αMePhe)LDTK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 16T, 17K, C18diacid)17RARDFVR 20R, 24R, WLLE(Aib)G-acid 27L, 28E, 29Aib, 30G Peptide H(Aib)QGTFTSDVSK 101 C20diacid γE- 17 Acid 2Aib, 10V, 190 (αMePhe)LDTK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 16T, 17K, C20diacid)17RAQDFVR 24R, 27V, WLVE(Aib)G-acid 28E, 29Aib, 30G Peptide H(Aib)QGTFTSDVSK 102 C18diacid γE- 17 Acid 2Aib, 10V, 191 (αMePhe)LDTK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 16T, 17K, C18diacid)17RAQDFVR 24R, 27V, WLVE(Aib)G-acid 28E, 29Aib, 30G Peptide H(Aib)QGTFTSDVSK 103 C18diacid γE- 17 Acid 2Aib, 10V, 192 (αMePhe)LDTK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 16T, 17K, C18diacid)17RAQDFVR 24R, 27L, WLL(Aib)E-acid 28Aib, 29E Peptide H(Aib)QGTFTSDVSK 104 C20diacid γE- 17 Acid 2Aib, 10V, 193 (αMePhe)LDTK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 16T, 17K, C20diacid)17RAQDFVR 24R, 27L, WLL(Aib)E-acid 28Aib, 29E Peptide H(Aib)QGTFTSDVSK 105 C20diacid γE- 17 Acid 2Aib, 10V, 194 (αMePhe)LDTK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-yE-γE- (O2Oc) 16T, 17K, C20diacid)17RAQDFVR 24R, 27L, WLL(Aib)E-acid 28Aib, 29E Peptide H(Aib)QGTFTSDVSK 106 C20diacid γE- 17 Acid 2Aib, 10V, 195 (αMePhe)LDTK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 16T, 17K, C20diacid)17RARDFVQ 20R, 27L, WLLE(Aib)G-acid 28E, 29Aib, 30G Peptide H(Aib)QGTFTSDVSK 107 C18diacid γE- 17 Acid 2Aib, 10V, 196 (αMePhe)LDSK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17K, 24R, C18diacid)17RAQDFVR 27I, 28Aib, WLI(Aib)E-acid 29E Peptide H(Aib)QGTFTSDVSK 108 C18diacid γE- 17 Acid 2Aib, 10V, 197 (αMePhe)LDTK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 16T, 17K, C18diacid)17RARDFVR 20R, 24R, WLL(Aib)E-acid 27L, 28Aib, 29E Peptide H(Aib)QGTFTSDVSK 109 C18diacid γE- 17 Acid 2Aib, 10V, 198 (αMePhe)LDTK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 16T, 17K, C18diacid)17RARDFIA 20R, 23I, WLL(Aib)E-acid 24A, 27L, 28Aib, 29E Peptide H(Aib)QGTFTSDVSK 110 C18diacid γE- 17 Acid 2Aib, 10V, 199 (αMePhe)LDTK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-yE- (O2Oc) 16T, 17K, C18diacid)17RARDFIA 20R, 23I, WLLE(Aib)G-acid 24A, 27L, 28E, 29Aib, 30G Peptide H(Aib)QGTFTSDVSK 111 C18diacid γE- 17 Acid 2Aib, 10V, 200 (αMePhe)LDTK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 16T, 17K, C18diacid)17RARDFVA 20R, 24A, WLLE(Aib)G-acid 27L, 28E, 29Aib, 30G Peptide H(Aib)QGTFTSDVSK 112 C18diacid γE- 17 Acid 2Aib, 10V, 201 (αMePhe)LDTK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 16T, 17K, C18diacid)17RARDFVA 20R, 24A, WLEA(Aib)G-acid 27E, 28A, 29Aib, 30G Peptide H(Aib)QGTFTSDVSK 113 C18diacid γE- 17 Acid 2Aib, 10V, 202 (αMePhe)LDTK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 16T, 17K, C18diacid)17RARDFVQ 20R, 27E, WLEA(Aib)G-acid 28A, 29Aib, 30G Peptide H(Aib)QGTFTSDVSK 418 C20diacid γE- 17 Acid 2(Aib), 10V, 407 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-yE- (O2Oc) 16T, 17K, C20diacid)17RAQDFVR 24R, 27E, WLEA(Aib)G-acid 28A, 29(Aib), 30G Peptide H(Aib)QGTFTSDVSK 419 C20diacid γE-γE- 17 Acid 2(Aib), 10V, 408 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE-yE- (O2Oc) 16T, 17K, C20diacid)17RAQDFVR 24R, 27E, WLEA(Aib)G-acid 28A, 29(Aib), 30G Peptide H(Aib)OGTFTSDVSK 420 C18diacid γE- 17 Acid 2(Aib), 10V, 409 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C18diacid)17RARDFVA 20R, 24A, WLL(Aib)TE-acid 27L, 28(Aib), 30E Peptide H(Aib)QGTFTSDVSK 421 C20diacid γE- 17 Acid 2(Aib), 10V, 410 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C20diacid)17RARDFVA 20R, 24A, WLL(Aib)TE-acid 27L, 28(Aib), 30E Peptide H(Aib)QGTFTSDVSK 422 C18diacid γE- 17 Acid 2(Aib), 10V, 411 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C18diacid)17RAQDFVA 24A, 27E, WLEAGG-acid 28A, 29G, 30G Peptide H(Aib)QGTFTSDVSK 423 C20diacid γE- 17 Acid 2(Aib), 10V, 412 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C20diacid)17RAQDFVA 24A, 27E, WLEAGG-acid 28A, 29G, 30G Peptide H(Aib)QGTFTSDVSK 424 C20diacid γE-γE- 17 Acid 2(Aib), 10V, 413 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-yE-γE- (O2Oc) 16T, 17K, C20diacid)17RAQDFVA 24A, 27E, WLEAGG-acid 28A, 29G, 30G Peptide H(Ab)QGTFTSDVSK 425 C18diacid γE- 17 Acid 2(Aib), 10V, 414 (αMePhe)LDKK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16K, 17K, C18diacid)17RARDFVR 20R, 24R, WLL(Aib)E-acid 27L, 28(Aib), 29E Peptide H(Aib)QGTFTSDVSK 426 C18diacid γE- 17 Acid 2(Aib), 10V, 415 (αMePhe)LESK(O2Oc-O2Oc- (O2Oc)- 13(αMePhe), γE- (O2Oc) 15€, 17K, C18diacid)17RAQDFVR 24R, 27E, WLEA(Aib)G-acid 28A, 29(Aib), 30G Peptide H(Aib)QGTFTSDVSK 427 C20diacid γE- 17 Acid 2(Aib), 10V, 416 (αMePhe)LESK(O2Oc-O2Oc- (O2Oc)- 13(αMePhe), γE- (O2Oc) 15E, 17K, C20diacid)17RAQDFVR 24R, 27E, WLEA(Aib)G-acid 28A, 29(Aib), 30G Peptide H(Aib)OGTFTSDVSK 428 C18diacid γE-γE- 17 Acid 2(Aib), 10V, 417 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE-γE- (O2Oc) 16T, 17K, C18diacid)17RAQDFVA 24A, 27E, WLEA(Aib)G-acid 28A, 29(Aib), 30G Peptide H(Aib)QGTFTSDVSK 429 C20diacid γE-γE- 17 Acid 2(Aib), 10V, 418 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE-γE- (O2Oc) 16T, 17K, C20diacid)17RAODFVA 24A, 27E, WLEA(Aib)G-acid 28A, 29(Aib), 30G Peptide H(Ab)QGTFTSDVSK 430 C18diacid γE- 17 Acid 2(Aib), 10V, 419 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C18diacid)17RAQDFVR 24R, 27E, WLE(Aib)E-acid 28(Aib), 29E Peptide H(Aib)QGTFTSDVSK 431 C18diacid γE- 17 Amide 2(Aib), 10V, 420 (αMePhe)LDKK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16K, 17K, C18diacid)17RAQDFVR 24R, 27L, WLL(Aib)E-amide 28(Aib), 29E Peptide H(Aib)QGTFTSDVSK 432 C18diacid γE- 17 Acid 2(Aib), 10V, 421 (αMePhe)LDRK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16R, 17K, C18diacid)17RAQDFVR 24R, 27L, WLL(Aib)TE-acid 28(Aib), 30E Peptide H(Aib)QGTFTSDVSK 433 C18diacid γE- 17 Amide 2(Aib), 10V, 422 (αMePhe)LDRK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16R, 17K, C18diacid)17RAQDFVR 24R, 27L, WLL(Aib)TE-amide 28(Aib), 30E Peptide H(Aib)QGTFTSDVSK 434 C18diacid γE- 17 Acid 2(Aib), 10V, 423 (αMePhe)LDKK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16K, 17K, C18diacid)17RAQDFVR 24R, 27K, WLK(Aib)TE-acid 28(Aib), 30E Peptide H(Aib)QGTFTSDVSK 435 C18diacid γE- 17 Acid 2(Aib), 10V, 424 (αMePhe)LDKK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16K, 17K, C18diacid)17RAQDFVR 24R, 27L, WLL(Aib)TK-acid 28(Aib), 30K Peptide H(Aib)QGTFTSDVSK 436 C18diacid γE- 17 Acid 2(Aib), 10V, 425 (αMePhe)LDKK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16K, 17K, C18diacid)17RAQDFVR 24R, 27K, WLKA(Aib)G-acid 28A, 29(Aib), 30G Peptide H(Aib)QGTFTSDVSK 437 C18diacid γE- 17 Acid 2(Aib), 10V, 426 (αMePhe)LDKK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16K, 17K, C18diacid)17RAQDFVR 24R, 27L, WLLR(Aib)K-acid 28R, 29(Aib), 30K Peptide H(Aib)QGTFTSDVSK 438 C18diacid γE- 17 Amide 2(Aib), 10V, 427 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C18diacid)17RARDFVQ 20R, 27L, WLLE(Aib)G-amide 28E, 29(Aib), 30G Peptide H(Aib)QGTFTSDVSK 439 C18diacid γE-γE- 17 Amide 2(Aib), 10V, 428 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE-γE- (O2Oc) 16T, 17K, C18diacid)17RARDFVQ 20R, 27L, WLLE(Aib)G-amide 28E, 29(Aib), 30G Peptide H(Alb)QGTFTSDVSK 440 C18diacid γE- 17 Amide 2(Aib), 10V, 429 (αMePhe)LDSK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 17K, 24R, C18diacid)17RAQDFVR 27E, 28A, WLEA(Alb)G-amide 29(Aib), 30G Peptide H(Aib)QGTFTSDVSK 441 C18diacid γE-γE- 17 Amide 2(Aib), 10V, 430 (αMePhe)LDSK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE-γE- (O2Oc) 17K, 24R, C18diacid)17RAQDFVR 27E, 28A, WLEA(Aib)G-amide 29(Aib), 30G Peptide H(Aib)QGTFTSDVSK 442 C18diacid γE-γE- 17 Amide 2(Aib), 10V, 431 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE-γE- (O2Oc) 16T, 17K, C18diacid)17RAQDFVA 24A, 27E, WLEA(Aib)G-amide 28A, 29(Aib), 30G Peptide H(Aib)QGTFTSDVSK 443 C18diacid γE- 17 Acid 2(Aib), 10V, 432 (αMePhe)LDSK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 17K, 24R, C18diacid)17RAQDFVR 25(Bip), 27L, (Bip)LL(Aib)E-acid 28(Aib), 29E Peptide H(Aib)QGTFTSDVSK 444 C18diacid γE- 17 Acid 2(Aib), 10V, 433 (αMePhe)LDSK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 17K, 24R, C18diacid)17RAQDFVR 25(1-Methyl- (1-Methyl-Trp)LL(Aib)E- Trp), 27L, acid 28(Aib), 29E Peptide H(Aib)OGTFTSDVSK 445 C18diacid γE- 17 Acid 2(Aib), 10V, 434 (αMePhe)LDSK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 17K, 24R, C18diacid)17RAQDFVR 25(5-BrTrp), (5-BrTrp)LL(Aib)E-acid 27L, 28(Aib), 29E Peptide H(Aib)OGTFTSDVSK 446 C18diacid γE- 17 Acid 2(Aib), 10V, 435 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C18diacid)17RARDFVQ 20R, 25(Aib), (Aib)LLE(Aib)G-acid 27L, 28E, 29(Aib), 30G Peptide H(Aib)QGTFTSDVSK 447 C18diacid γE- 17 Amide 2(Aib), 10V, 436 (αMePhe)LDRK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16R, 17K, C18diacid)17RAQDFVR 24R, 27V, WLV(Aib)E-amide 28(Aib), 29E Peptide H(Aib)QGTFTSDVSK 448 C20diacid γE- 17 Amide 2(Aib), 10V, 437 (αMePhe)LDRK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16R, 17K, C20diacid)17RAQDFVR 24R, 27V, WLV(Aib)E-amide 28(Aib), 29E Peptide H(Aib)QGTFTSDVSK 449 C18diacid γE- 17 Amide 2(Aib), 10V, 438 (αMePhe)LDKK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16K, 17K, C18diacid)17RAQDFVR 24R, 27E, WLEA(Aib)G-amide 28A, 29(Aib), 30G Peptide H(Aib)QGTFTSDVSK 450 C18diacid γE- 17 Amide 2(Aib), 10V, 439 (αMePhe)LDRK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16R, 17K, C18diacid)17RAQDFVR 24R, 27L, WLL(Aib)E-amide 28(Aib), 29E Peptide H(Aib)QGTFTSDVSK 451 C20diacid γE- 17 Acid 2(Aib), 10V, 440 (αMePhe)LDKK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16K, 17K, C20diacid)17RARDFVR 20R, 24R, WLL(Aib)E-acid 27L, 28(Aib), 29E Peptide H(Aib)QGTFTSDVSK 452 C20diacid γE- 17 Amide 2(Aib), 10V, 441 (αMePhe)LDKK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16K, 17K, C20diacid)17RAQDFVR 24R, 27L, WLL(Aib)E-amide 28(Aib), 29E Peptide H(Aib)OGTFTSDVSK 453 C18diacid γE- 17 Amide 2(Aib), 10V, 442 (αMePhe)LDKK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16K, 17K, C18diacid)17RAQDFVR 24R, 27L, WLLE(Aib)G-amide 28E, 29(Aib), 30G Peptide H(Aib)QGTFTSDVSK 454 C18diacid γE- 17 Amide 2(Aib), 10V, 443 (αMePhe)LDKK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16K, 17K, C18diacid)17RARDFVR 20R, 24R, WLL(Aib)E-amide 27L, 28(Aib), 29E Peptide H(Aib)QGTFTSDVSK 455 C18diacid γE- 17 Acid 2(Aib), 10V, 444 (αMePhe)LETK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 15E, 16T, C20diacid)17RARDFVQ 17K, 20R, WLLE(Aib)G-acid 27L, 28E, 29(Aib), 30G Peptide H(Aib)QGTFTSDVSK 456 C18diacid γE- 17 Acid 2(Aib), 10V, 445 (αMePhe)LETK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-yE- (O2Oc) 15E, 16T, C18diacid)17RARDFVQ 17K, 20R, WLLE(Aib)G-acid 27L, 28E, 29(Aib), 30G Peptide H(Aib)QGTFTSDVSK 457 C18diacid γE-γE- 17 Amide 2(Aib), 10V, 446 (αMePhe)LDRK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE-γE- (O2Oc) 16R, 17K, C18diacid)17RAQDFVR 24R, 27V, WLV(Aib)E-amide 28(Aib), 29E Peptide H(Aib)QGTFTSDVSK 458 C20diacid γE-γE- 17 Amide 2(Aib), 10V, 447 (αMePhe)LDRK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-vE-yE- (O2Oc) 16R, 17K, C20diacid)17RAQDFVR 24R, 27V, WLV(Aib)E-amide 28(Aib), 29E Peptide H(Aib)QGTFTSDVSK 459 C18diacid γE-γE- 17 Acid 2(Aib), 10V, 448 (αMePhe)LDKK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE-γE- (O2Oc) 16K, 17K, C18diacid)17RARDFVR 20R, 24R, WILL(Aib)E-acid 27L, 28(Aib), 29E Peptide H(Aib)QGTFTSDVSK 460 C20diacid γE-γE- 17 Acid 2(Aib), 10V, 449 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE-γE- (O2Oc) 16T, 17K, C20diacid)17RARDFVQ 20R, 27L, WLLE(Aib)G-acid 28E, 29(Aib), 30G Peptide H(Aib)OGTFTSDVSK 461 C18diacid γE-γE- 17 Acid 2(Aib), 10V, 450 (αMePhe)LDKK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE-γE- (O2Oc) 16K, 17K, C18diacid)17RAQDFVR 24R, 27L, WLLE(Aib)G-acid 28E, 29(Aib), 30G Peptide H(Ab)QGTFTSDVSK 462 C20diacid γE- 17 Amide 2(Aib), 10V, 451 (αMePhe)LDKK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16K, 17K, C20diacid)17RARDFVL 20R, 24L, WLL(Aib)E-amide 27L, 28(Aib), 29E Peptide H(Aib)QGTFTSDVSK 463 C20diacid γE- 17 Amide 2(Aib), 10V, 452 (αMePhe)LDKK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16K, 17K, C20diacid)17RALDFVR 20L, 24R, WLL(Aib)E-amide 27L, 28(Aib), 29E Peptide H(Aib)QGTFTSDVSK 464 C20diacid γE- 17 Amide 2(Aib), 10V, 453 (αMePhe)LDKK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16K, 17K, C20diacid)17RAQDFVR 24R, 27L, WLLE(Aib)G-amide 28E, 29(Aib), 30G Peptide H(Ab)QGTFTSDVSK 465 C20diacid γE- 17 Amide 2(Aib), 10V, 454 (αMePhe)LDKK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16K, 17K, C20diacid)17RAQDFVR 24R, 27E, WLEA(Aib)G-amide 28A, 29(Aib), 30G Peptide H(Aib)QGTFTSDVSK 466 C20diacid γE-γE- 17 Amide 2(Aib), 10V, 455 (αMePhe)LDKK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE-yE- (O2Oc) 16K, 17K, C20diacid)17RAQDFVR 24R, 27L, WLL(Aib)E-amide 28(Aib), 29E Peptide H(Aib)OGTFTSDVSK 467 C20diacid γE- 17 Amide 2(Aib), 10V, 456 (αMePhe)LDRK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16R, 17K, C20diacid)17RAQDFVR 24R, 27L, WLL(Aib)E-amide 28(Aib), 29E Peptide H(Aib)QGTFTSDVSK 468 C20diacid γE- 17 Amide 2(Aib), 10V, 457 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C20diacid)17RARDFVQ 20R, 27L, WLLE(Aib)G-amide 28E, 29(Aib), 30G Peptide H(Aib)QGTFTSDVSK 469 C20diacid γE-γE- 17 Amide 2(Aib), 10V, 458 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE-γE- (O2Oc) 16T, 17K, C20diacid)17RARDFVQ 20R, 27L, WLLE(Aib)G-amide 28E, 29(Aib), 30G Peptide H(Aib)QGTFTSDVSK 470 C18diacid γE- 17 Amide 2(Aib), 10V, 459 (αMePhe)LDKK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-yE- (O2Oc) 16K, 17K, C18diacid)17RAQDFVR 24R, 27L, WLLAE-amide 28A, 29E Peptide H(Aib)OGTFTSDVSK 471 C20diacid γE- 17 Amide 2(Aib), 10V, 460 (αMePhe)LDKK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16K, 17K, C20diacid)17RAQDFVR 24R, 27L, WLLAE-amide 28A, 29E Peptide H(Aib)QGTFTSDVSK 472 C18diacid γE- 17 Amide 2(Aib), 10V, 461 (αMePhe)LDRK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-yE- (O2Oc) 16R, 17K, C18diacid)17RAQDFVR 24R, 27L, WLLAE-amide 28A, 29E Peptide H(AIb)QGTFTSDVSK 473 C18diacid γE- 17 Acid 2(Aib), 10V, 462 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C18diacid)17RARDFVQ 20R, 27L, WLLEAG-acid 28E, 29A, 30G Peptide H(Aib)QGTFTSDVSK 474 C18diacid γE-γE- 17 Amide 2(Aib), 10V, 463 (αMePhe)LDSK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE-γE- (O2Oc) 17K, 27L, C18diacid)17RAQDFVQ 28(Aib) WLL(Aib)T-amide Peptide H(Aib)QGTFTSDVSK 475 C18diacid γE- 17 Acid 2(Aib), 10V, 464 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-yE- (O2Oc) 16T, 17K, C18diacid)17RAQDFVQ 27L, 28E, WLLE(Aib)G-acid 29(Aib), 30G Peptide H(Aib)OGTFTSDVSK 476 C18diacid γE-γE- 17 Acid 2(Aib), 10V, 465 (αMePhe)LDLK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE-γE- (O2Oc) 16L, 17K, C18diacid)17RAQDFVQ 27L, 28(Aib) WLL(Aib)T-acid Peptide H(Aib)QGTFTSDVSK 477 C18diacid γE- 17 Amide 2(Aib), 10V, 466 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C18diacid)17RAQDFVQ 27L, 28E, WLLE(Aib)G-amide 29(Aib), 30G Peptide H(Aib)QGTFTSDVSK 478 C20diacid yE- 17 Amide 2(Aib), 10V, 467 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C20diacid)17RAQDFVQ 27L, 28E, WLLE(Aib)G-amide 29(Aib), 30G Peptide H(Aib)QGTFTSDVSK 479 C18diacid γE-γE- 17 Amide 2(Aib), 10V, 468 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-yE-γE- (O2Oc) 16T, 17K, C18diacid)17RAQDFVQ 27L, 28E, WLLE(Aib)G-amide 29(Aib), 30G Peptide H(Aib)OGTFTSDVSK 480 C20diacid γE-γE- 17 Amide 2(Aib), 10V, 469 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE-γE- (O2Oc) 16T, 17K, C20diacid)17RAQDFVQ 27L, 28E, WLLE(Alb)G-amide 29(Aib), 30G Peptide H(Aib)QGTFTSDVSK 481 C20diacid γE- 17 Amide 2(Aib), 10V, 470 (αMePhe)LDKK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16K, 17K, C20diacid)17RARDFVQ 20R, 27L, WLL(Aib)E-amide 28(Aib), 29E Peptide H(Aib)QGTFTSDVSK 482 C20diacid γE- 17 Amide 2(Aib), 10V, 471 (αMePhe)LDRK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16R, 17K, C20diacid)17RARDFVQ 20R, 27L, WLL(Aib)E-amide 28(Aib), 29E Peptide H(Aib)QGTFTSDVSK 483 C18diacid γE- 17 Amide 2(Aib), 10V, 472 (αMePhe)LDKK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16K, 17K, C18diacid)17RARDFVQ 20R, 27L, WLL(Aib)E-amide 28(Aib), 29E Peptide H(Aib)QGTFTSDVSK 484 C18diacid γE- 17 Amide 2(Aib), 10V, 473 (αMePhe)LDRK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16R, 17K, C18diacid)17RARDFVQ 20R, 27L, WLL(Aib)E-amide 28(Aib), 29E Peptide H(Aib)QGTFTSDVSK 485 C18diacid γE- 17 Amide 2(Aib), 10V, 474 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C18diacid)17RARDFVQ 20R, 27L, WLLA(Aib)G-amide 28A, 29(Aib), 30G Peptide H(Aib)QGTFTSDVSK 486 C20diacid γE- 17 Amide 2(Aib), 10V, 475 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C20diacid)17RARDFVQ 20R, 27L, WLLA(Aib)G-amide 28A, 29(Aib), 30G Peptide H(Aib)OGTFTSDVSK 487 C18diacid γE- 17 Amide 2(Aib), 10V, 476 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C18diacid)17RAQDFVR 24R, 27L, WILLA(Aib)G-amide 28A, 29(Aib), 30G Peptide H(Aib)QGTFTSDVSK 488 C20diacid γE- 17 Amide 2(Aib), 10V, 477 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C20diacid)17RAQDFVR 24R, 27L, WLLA(Aib)G-amide 28A, 29(Aib), 30G Peptide H(Aib)QGTFTSDVSK 489 C18diacid γE- 17 Åmide 2(Aib), 10V, 478 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C18diacid)17RAQDFVR 24R, 27L, WLLE(Aib)K-amide 28E, 29(Aib), 30K Peptide H(Aib)QGTFTSDVSK 490 C20diacid γE- 17 Amide 2(Aib), 10V, 479 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-yE- (O2Oc) 16T, 17K, C20diacid)17RAQDFVR 24R, 27L, WLLE(Aib)K-amide 28E, 29(Aib), 30K Peptide H(Aib)OGTFTSDVSK 491 C18diacid γE- 17 Amide 2(Aib), 10V, 480 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C18diacid)17RARDFVQ 20R, 27L, WLLE(Aib)K-amide 28E, 29(Aib), 30K Peptide H(Ab)QGTFTSDVSK 492 C20diacid γE- 17 Amide 2(Aib), 10V, 481 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C20diacid)17RARDFVQ 20R, 27L, WLLE(Aib)K-amide 28E, 29(Aib), 30K Peptide H(Aib)OGTFTSDVSK 493 C18diacid γE- 17 Acid 2(Aib), 10V, 482 (αMePhe)LESK(O2Oc-O2Oc- (O2Oc)- 13(αMePhe), γE- (O2Oc) 15E, 17K, C18diacid)17RAQDFVQ 27L, 28(Aib), WLL(Aib)E-acid 29E Peptide H(Aib)QGTFTSDVSK 494 C18diacid γE- 17 Acid 2(Aib), 10V, 483 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C18diacid)17RAQDFVQ 27L, 28(Aib), WLL(Aib)E-acid 29E Peptide H(Ab)QGTFTSDVSK 495 C20diacid γE- 17 Acid 2(Aib), 10V, 484 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K C20diacid)17RAQDFVQ 27L, 28(Aib), WLL(Aib)E-acid 29E Peptide H(Aib)QGTFTSDVSK 496 C20diacid γE- 17 Amide 2(Aib), 10V, 485 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-yE- (O2Oc) 16T, 17K, C20diacid)17RAQDFVQ 27L, 28(Aib), WLL(Aib)E-amide 29E Peptide H(Aib)QGTFTSDVSK 497 C20diacid γE- 17 Acid 2(Aib), 10V, 486 (αMePhe)LDLK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16L, 17K, C20diacid)17RAQDFVR 24R, 27L, WLL(Aib)E-acid 28(Aib), 29E Peptide H(Aib)QGTFTSDVSK 498 C18diacid γE- 17 Acid 2(Aib), 10V, 487 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C18diacid)17RARDFVQ 20R, 27L, WLL(Aib)TE-acid 28(Aib), 30E Peptide H(Aib)QGTFTSDVSK 499 C20diacid γE- 17 Acid 2(Aib), 10V, 488 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-yE- (O2Oc) 16T, 17K, C20diacid)17RARDEVO 20R, 27L, WLL(Aib)TE-acid 28(Aib), 30E Peptide H(Aib)QGTFTSDVSK 500 C18diacid γE- 17 Amide 2(Aib), 10V, 489 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-yE- (O2Oc) 16T, 17K, C18diacid)17RARDFVQ 20R, 27L, WLL(Aib)TE-amide 28(Aib), 30E Peptide H(Aib)QGTFTSDVSK 501 C20diacid γE- 17 Amide 2(Aib), 10V, 490 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C20diacid)17RARDFVQ 20R, 27L, WLL(Aib)TE-amide 28(Aib), 30E Peptide H(Aib)QGTFTSDVSK 502 C18diacid γE- 17 Acid 2(Aib), 10V, 491 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-yE- (O2Oc) 16T, 17K, C18diacid)17RARDFVR 20R, 24R, WLL(Aib)TE-acid 27L, 28(Aib), 30E Peptide H(Aib)QGTFTSDVSK 503 C20diacid γE- 17 Acid 2(Aib), 10V, 492 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C20diacid)17RARDFVR 20R, 24R, WLL(Aib)TE-acid 27L, 28(Aib), 30E Peptide H(Ab)QGTFTSDVSK 504 C18diacid γE- 17 Acid 2(Aib), 10V, 493 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C18diacid)17RAQDFVR 24R, 27L, WLLR(Aib)K-acid 28R, 29(Aib), 30K Peptide H(Aib)QGTFTSDVSK 505 C20diacid γE- 17 Acid 2(Aib), 10V, 494 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C20diacid)17RAQDFVR 24R, 27L, WLLR(Aib)K-acid 28R, 29(Aib), 30K Peptide H(Aib)QGTFTSDVSK 506 C18diacid γE- 17 Amide 2(Aib), 10V, 495 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C18diacid)17RAQDFVR 24R, 27L, WLLR(Aib)K-amide 28R, 29(Aib), 30K Peptide H(Aib)QGTFTSDVSK 507 C20diacid γE- 17 Amide 2(Aib), 10V, 496 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-yE- (O2Oc) 16T, 17K, C20diacid)17RAQDFVR 24R, 27L, WLLR(Aib)K-amide 28R, 29(Aib), 30K Peptide H(Aib)QGTFTSDVSK 508 C18diacid γE- 17 Acid 2(Aib), 10V, 497 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C18diacid)17RAQDFVR 24R, 27L, WLLR(Aib)A-acid 28R, 29(Aib), 30A Peptide H(Aib)QGTFTSDVSK 509 C20diacid γE- 17 Acid 2(Aib), 10V, 498 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C20diacid)17RAQDFVR 24R, 27L, WLLR(Aib)A-acid 28R, 29(Aib), 30A Peptide H(Aib)QGTFTSDVSK 510 C18diacid γE- 17 Acid 2(Aib), 10V, 499 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C18diacid)17RAQDFVQ 27L, 28R, WLLR(Aib)A-acid 29(Aib), 30A Peptide H(Aib)QGTFTSDVSK 511 C20diacid γE- 17 Acid 2(Aib), 10V, 500 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C20diacid)17RAQDFVQ 27L, 28R, WLLR(Aib)A-acid 29(Aib), 30A Peptide H(Aib)OGTFTSDVSK 512 C18diacid γE- 17 Acid 2(Aib), 10V, 501 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C18diacid)17RARDFVQ 20R, 27L, WLLR(Aib)A-acid 28R, 29(Aib), 30A Peptide H(Aib)QGTFTSDVSK 513 C20diacid γE- 17 Acid 2(Aib), 10V, 502 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C20diacid)17RARDFVQ 20R, 27L, WLLR(Aib)A-acid 28R, 29(Aib), 30A Peptide H(Aib)QGTFTSDVSK 514 C20diacid γE- 17 Acid 2(Aib), 10V, 503 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C20diacid)17RAQDFVR 24R, 27L, WLLE(Aib)K-acid 28E, 29(Aib), 30K Peptide H(Aib)QGTFTSDVSK 515 C20diacid γE- 17 Acid 2(Aib), 10V, 504 (αMePhe)LESK(O2Oc-O2Oc- (O2Oc)- 13(αMePhe), γE- (O2Oc) 15E, 17K, C20diacid)17RAQDFVR 24R, 27L, WLLE(Aib)K-acid 28E, 29(Aib), 30K Peptide H(Aib)QGTFTSDVSK 516 C20diacid γE- 17 Amide 2(Aib), 10V, 505 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C20diacid)17RAQDFVQ 27L, 28E, WLLE(Aib)K-amide 29(Aib), 30K Peptide H(Aib)QGTFTSDVSK 517 C20diacid γE- 17 Acid 2(Aib), 10V, 506 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C20diacid)17RARDFVA 20R, 24A, WLLE(Aib)G-acid 27L, 28E, 29(Aib), 30G Peptide H(Aib)QGTFTSDVSK 518 C20diacid γE- 17 Amide 2(Aib), 10V, 507 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C20diacid)17RARDFVA 20R, 24A, WLLE(Aib)G-amide 27L, 28E, 29(Aib), 30G Peptide H(Aib)QGTFTSDVSK 519 C20diacid γE- 17 Amide 2(Aib), 10V, 508 (αMePhe)LESK(O2Oc-O2Oc- (O2Oc)- 13(αMePhe), γE- (O2Oc) 15E, 17K, C20diacid)17RAQDFVR 24R, 27V, WLVE(Aib)G-amide 28E, 29(Aib), 30G Peptide H(Ab)QGTFTSDVSK 520 C20diacid γE- 17 Acid 2(Aib), 10V, 509 (αMePhe)LESK(O2Oc-O2Oc- (O2Oc)- 13(αMePhe), γE- (O2Oc) 15E, 17K, C20diacid)17RAQDFVR 24R, 27L, WILL(Aib)TE-acid 28(Aib), 30E Peptide H(Aib)QGTFTSDVSK 521 C20diacid γE- 17 Acid 2(Aib), 10V, 510 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C20diacid)17RARDFVR 20R, 24R, WLL(Aib)E-acid 27L, 28(Aib), 29E Peptide H(AIb)QGTFTSDVSK 522 C20diacid γE- 17 Amide 2(Aib), 10V, 511 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C20diacid)17RARDFVR 20R, 24R, WLL(Aib)E-amide 27L, 28(Aib), 29E Peptide H(Aib)QGT(αMePhe)TS 523 C18diacid γE- 17 Amide 2(Aib), 512 DVSK(αMePhe)LDTK (O2Oc)- 6(αMePhe), (O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)17RAQD  13(αMePhe), (αMePhe)VRWLLA(Aib)G- 16T, 17K, amide 22(αMePhe), 24R, 27L, 28A, 29(Aib), 30G Peptide H(Aib)QGT(αMePhe)TS 524 C18diacid γE- 17 Amide 2(Aib), 513 DVSK(αMePhe)LDTK (O2Oc)- 6(αMePhe) (O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)17RARD  13(αMePhe), (αMePhe)VQWLLA(Aib)G- 16T, 17K, amide 20R 22(αMePhe), 27L, 28A, 29(Aib), 30G Peptide H(Aib)QGTFTSDVSK 525 C18diacid γE- 17 Amide 2(Aib), 10V, 514 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C18diacid)17AARDFVQ 18A, 20R, WLLE(Aib)G-amide 27L, 28E, 29(Aib), 30G Peptide H(Aib)QGTFTSDVSK 526 C20diacid γE- 17 Amide 2(Aib), 10V, 515 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE- (O2Oc) 16T, 17K, C20diacid)17AARDFVQ 18A, 20R, WLLE(Aib)G-amide 27L, 28E, 29(Aib), 30G Peptide H(Aib)QGTFTSDVSK 527 C20diacid γE- 17 Amide 2(Aib), 10V, 516 (αMePhe)LESK(O2Oc-O2Oc- (O2Oc)- 13(αMePhe), γE- (O2Oc) 15E, 17K, C20diacid)17RAQDFVR 24R, 27L, WLLA(Aib)G-amide 28A, 29(Aib), 30G Peptide H(Aib)QGTFTSDVSK 528 C18diacid γE-γE- 17 Amide 2(Aib), 10V, 517 (αMePhe)LEAK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE-γE- (O2Oc) 15E, 16A, C18diacid)17AAREFIAW 17K, 18A, LLET-amide 20R, 21E, 23I, 24A, 27L, 28E Peptide H(Aib)QGTFTSDVSK 529 C18diacid γE-γE- 17 Acid 2(Aib), 10V, 518 (αMePhe)LDTK(O2Oc- (O2Oc)- 13(αMePhe), O2Oc-γE-γE- (O2Oc) 16T, 17K, 20R, 27L C18diacid)17RARDFVQ 28E, 29(Aib), WLLE(Aib)G-acid 30G Peptide H(Aib)QGTFTSDVSK 530 C18diacid γE-γE- 17 Acid 2(Aib), 10V, 519 (αMePhe)LDTK(γE-γE- (O2Oc)- 13(αMePhe), O2Oc-O2Oc-γE-γE- (O2Oc)- 16T, 17K, C18diacid)17RARDFVQ γE-γE 20R, 27L, WLLE(Aib)G-acid 28E, 29(Aib), 30G Peptide H(Ab)QGTFTSDVSK 531 C20diacid γE-γE- 17 Acid 2(Aib), 10V, 520 (αMePhe)LDTK(γE-γE- (O2Oc)- 13(αMePhe), O2Oc-O2Oc-γE-γE- (O2Oc)- 16T, 17K, C20diacid)17RARDFVQ γE-γE 20R, 27L, WLLE(Aib)G-acid 28E, 29(Aib), 30G

In some aspects, the peptide comprises the sequence: H-X2-X3-G-X5-X6-T-S-D-X10-S-X12-X13-L-X15-X16-X17-X18-X19-X20-X21-X22-X23-X24-X25-X26-X27-X28-X29-X30-X31-Z, wherein X2 is S, Aminoisobutyric acid (Aib), αMethyl-Serine (αMeS), D-serine (dSer), 1-aminocyclopropane-1-carboxylic acid (Acpr), or S, 1-aminocyclobutane-1-carboxylic acid (Acbu), X3 is Q, H, αMethyl-Glutamine (αMeGln), N-Methyl-Glutamine (N-MeGln), D-glutamine (dGln) or β-dimethylglutamine (β-dimethylGln), X5 is T or S, X6 is F or αMethyl-Phenylalanine (αMePhe), X10 is Y or V, X12 is K, E, or R, X13 is Y, αMePhe, or Aib, X15 is D or E, X16 is S, T, E, or Aib, X17 is R, Q, or E, X18 is R, A, Aib, or S, X19 is A or V, X20 is Q or K, wherein the K can comprise an acyl moiety and/or can be lipidated, X21 is D or L, X22 is F or αMethyl-Phenylalanine (αMePhe), X23 is V or I, X24 is Q, E, A, or R, X25 is W, Aib, or S, X26 is L or I, X27 is M, A, L, E, I, or V, X28 is N, E, (PEG)4, Aib, S, or A, X29 is T, not present, E, or G, X30 is not present, E, T, or G, X31 is not present or G, and Z is amide or acid (SEQ ID NO: 413), wherein the peptide does not comprise SEQ ID NO: 1.

In some aspects, the residue at position 20 is acylated. In some aspects, the residue at position 20 is lipidated. In some aspects, the lipid is selected from the group consisting of a palmitoyl group, stearoyl group, lauryl group, myristoyl group, margaroyl group, octadecanedioic acid (C18diacid), and icosanedioic acid (C20diacid). In some aspects, the lipid is selected from the group consisting of a stearoyl group, octadecanedioic acid (C18diacid), and icosanedioic acid (C20diacid).

In some aspects, the lipid attached to the residue at position 20 is attached via a linker. In some aspects, the linker is selected from the group consisting of (O2Oc), (O2Oc)-(O2Oc), (O2Oc)-γE-(O2Oc), (PEG)2-(PEG)2-γE-γE, (PEG)2-γE-(PEG)2-γE, γE, γE-(O2Oc), γE-(O2Oc)-(O2Oc), γE-(O2Oc)-γE-(O2Oc), γE-(PEG)2-(PEG)2, γE-(PEG)2-γE-(PEG)2, γE-(PEG)4, γE-γE, γE-γE-(O2Oc), γE-γE-(O2Oc)-(O2Oc), γE-γE-(PEG)12, γE-γE-(PEG)2-(PEG)2, γE-γE-(PEG)2-γE-γE, γE-γE-(PEG)4, and γE-γE-(PEG)8. In some aspects, the linker is selected from the group consisting of γE, γE-γE, γE-γE-(O2Oc), γE-(O2Oc)-(O2Oc), γE-γE-(O2Oc)-(O2Oc), γE-(O2Oc), γE-γE-(PEG)2-(PEG)2, γE-(O2Oc)-γE-(O2Oc), γE-(PEG)4, γE-γE-(PEG)4, (O2Oc)-γE-(O2Oc), (O2Oc)-(O2Oc), and (O2Oc).

In some aspects, the peptide comprises the sequence: H-Aminoisobutyric acid (Aib)-Q-G-T-F-T-S-D-X10-S-X12-αMethyl-Phenylalanine (αMePhe)-L-D-X16-X17-X18-A-K-D-F-V-X24-W-X26-X27-X28-X29-X30-Z, wherein X10 is V or Y, X12 is K or E, X16 is S or Aib, X17 is R or E, X18 is R or A, X24 is A, R, or Q, X26 is L or I, X27 is E, L, A, or I, X28 is A, E, Aib, S, or N, X29 is G, Aib, T, or E, X30 is G, E, T, or not present, and Z is amide or acid (SEQ ID NO: 414).

In some aspects, the lysine at position 20 is acylated. In some aspects, the lysine at position 20 is lipidated. In some aspects, the lipid is selected from the group consisting of a palmitoyl group, stearoyl group, lauryl group, myristoyl group, margaroyl group, octadecanedioic acid (C18diacid), and icosanedioic acid (C20diacid). In some aspects, the lipid is octadecanedioic acid (C18diacid).

In some aspects, the lipid is linked to the lysine at position 20 via a linker. In some aspects, the linker is selected from the group consisting of (O2Oc), (O2Oc)-(O2Oc), (O2Oc)-γE-(O2Oc), (PEG)2-(PEG)2-γE-γE, (PEG)2-γE-(PEG)2-γE, γE, γE-(O2Oc), γE-(O2Oc)-(O2Oc), γE-(O2Oc)-γE-(O2Oc), γE-(PEG)2-(PEG)2, γE-(PEG)2-γE-(PEG)2, γE-(PEG)4, γE-γE, γE-γE-(O2Oc), γE-γE-(O2Oc)-(O2Oc), γE-γE-(PEG)12, γE-γE-(PEG)2-(PEG)2, γE-γE-(PEG)2-γE-γE, γE-γE-(PEG)4, and γE-γE-(PEG)8. In some aspects, the linker is selected from the group consisting of γE, γE-(O2Oc)-(O2Oc), and γE-γE(O2Oc)-(O2Oc)-γE-γE.

In some aspects, the peptide comprises any one of SEQ ID NOs: 207-347 and 532-537. In some aspects, the peptide comprises SEQ ID NO: 228. In some aspects, the peptide comprises SEQ ID NO: 233.

In some aspects, the peptide has the structure of any one of the structures depicted in FIGS. 4A-4B. In some aspects, the peptide has the structure of FIG. 4A. In some aspects, the peptide has the structure of FIG. 4B.

In some aspects, the peptide is any one of the peptides in Table 2.

TABLE 2 Peptides Modified at Position 20 Linker Sequence SEQ Aibumin (described Acyl- modification ID binding N→C ation C- with respect Peptide Sequence NO moiety term) site term. to glucagon Peptide H(Aib)HGS(αMePhe)TS 207 C18diacid γE- 20 Amide 2Aib, 3H, 5S, 203 DVSK(αMePhe)LDSQAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)20DFVQWIA 13αMePhe, NT-amide 17Q, 18A, 20K, 26I, 27A Peptide H(Aib)QGT(αMePhe)TS 208 C18diacid γE- 20 Amide 2Aib, 5S, 204 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)20DFVQWIA 13αMePhe, NT-amide 18A, 20K, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 209 C18diacid γE- 20 Amide 2Aib, 3H, 5S, 205 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE- (O2OC) 10V, C18diacid)20DFVQWIA 13αMePhe, NT-amide 18A, 20K, 26I ,27A Peptide H(Aib)HGS(αMePhe)TS 210 C18diacid γE- 20 Amide 2Aib, 3H, 5S, 206 DVSK(αMePhe)LDSR (O2Oc)- 6αMePhe, (Aib)AK(O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)20DFVQWIA 13αMePhe, NT-amide 18Aib, 20K, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 211 C18diacid γE- 20 Amide 2Aib, 3H, 5S, 207 DVSK(αMePhe)LDSQAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)20DFVQ(Aib) 13αMePhe, IANT-amide 17Q, 18A, 20K, 25Aib, 26I, 27A Peptide H(Aib)QGTFTSDVSK 212 C18diacid γE 20 Amide 2Aib, 10V, 208 (αMePhe)LDSRAAK(γE- 13αMePhe, C18diacid)20DFVQWIA 18A, 20K, NT-amide 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 213 C18diacid γE- 20 Amide 2Aib, 3H, 5S, 209 DVSK(αMePhe)LDSQAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE- (O2Oc) 10V C18diacid)20DFVEWIA 13αMePhe, NT-amide 17Q, 18A, 20K, 24E, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 214 C18diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 210 DVSK(αMePhe)LDSQAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE-γE- (O2Oc) 10V, C18diacid)20DFVEWIA 13αMePhe, NT-amide 170,18A, 20K, 24E, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 215 C20diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 211 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE-γE- (O2Oc) 10V, C20diacid)20DFVQWIA 13αMePhe, NT-amide 18A, 20K, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 216 C20diacid γE- 20 Amide 2Aib, 3H, 5S, 212 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE- (O2Oc) 10V, C20diacid)20DFVEWIA 13αMePhe, NT-amide 18A, 20K, 24E, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 217 C20diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 213 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE-γE- (O2Oc) 10V, C20diacid)20DFVEWIA 13αMePhe, NT-amide 18A, 20K, 24E, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 218 C20diacid γE- 20 Amide 2Aib, 3H, 5S, 214 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE- (O2Oc) 10V, C20diacid)20DFVQWIA 13αMePhe, NT-amide 18A, 20K, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 219 C20diacid γE- 20 Amide 2Aib, 3H, 5S, 215 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE- (O2Oc) 10V, C20diacid)20D 13αMePhe, (αMePhe)VQWIANT- 18A, 20K, amide 22αMePhe, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 220 C20diacid γE- 20 Amide 2Aib, 3H, 5S, 216 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE- (O2Oc) 10V, C20diacid)20D 13αMePhe, (αMePhe)VEWIANT- 18A, 20K, amide 22αMePhe, 24E, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 221 C20diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 217 DVSK(αMePhe)LDSR (O2Oc)- 6αMePhe, (Aib)AK(O2Oc-O2Oc-γE- (O2Oc) 10V, γE- 13αMePhe, C20diacid)20DFVQWIA 18Aib, 20K, NT-amide 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 222 C20diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 218 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE-γE- (O2Oc) 10V, C20diacid)20DFVQWIA 13αMePhe, NTG-amide 18A, 20K, 26I, 27A, 30G Peptide H(Aib)HGS(αMePhe)TS 223 C20diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 219 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE-γE- (O2Oc) 10V, C20diacid)20DFVQWIA 13αMePhe, NTGG-amide 18A, 20K, 26I, 27A, 30G, 31G Peptide H(Aib)HGS(αMePhe)TS 224 C20diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 220 DVSK(αMePhe)LDSR (O2Oc)- 6αMePhe, (Aib)AK(O2Oc-O2Oc- (O2Oc) 10V, γE-γE- 13αMePhe, C20diacid)20DFVQ(Aib) 18Aib, 20K, IANT-amide 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 225 C20diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 221 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE-γE- (O2Oc) 10V, C20diacid)20DFVQ(Aib) 13αMePhe, IANT-amide 18A, 20K, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 226 C18diacid γE- 20 Amide 2Aib, 3H, 5S, 222 DVSK(αMePhe)LDSQAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)20DFVQSIAN 13αMePhe, T-amide 17Q, 18A, 20K, 25S, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 227 C18diacid γE- 20 Amide 2Aib, 3H, 5S, 223 DVSK(αMePhe)LDSR (O2Oc)- 6αMePhe, (Aib)AK(O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)20DFVQSIAN 13αMePhe, T-amide 18Aib, 20K, 25S, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 228 C18diacid γE- 20 Amide 2Aib, 3H, 5S, 224 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 229 C18diacid γE- 20 Amide 2Aib, 3H, 5S, 225 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANTGG- 18A, 20K, amide 22αMePhe, 25Aib, 26I, 27A, 30G, 31G Peptide H(Aib)HGS(αMePhe)TS 230 C18diacid γE- 20 Amide 2Aib, 3H, 5S, 226 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)20D(αMePhe) 13αMePhe, VE(Aib)IANT-amide 18A, 20K, 22αMePhe, 24E, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 231 C18diacid γE- 20 Amide 2Aib, 3H, 5S, 227 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)20D(αMePhe) 13αMePhe, IA(Aib)IANT-amide 18A, 20K, 22αMePhe, 231, 24A, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 232 C20diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 228 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE-γE- (O2Oc) 10V, C20diacid)20D(αMePhe) 13αMePhe, VQWIANT-amide 18A, 20K, 22αMePhe, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 233 C20diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 229 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE-γE- (O2Oc) 10V, C20diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 234 C18diacid γE- 20 Amide 2Aib, 3H, 5S, 230 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)20D(αMePhe) 13αMePhe, IAWIANT-amide 18A, 20K, 22αMePhe, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 235 C18diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 231 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE-γE- (O2Oc) 10V, C18diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 236 C20diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 232 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE-γE- (O2Oc) 10V, C20diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANTGG- 18A, 20K, amide 22αMePhe, 25Aib, 26I, 27A, 30G, 31G Peptide H(Aib)HGS(αMePhe)TS 237 C20diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 233 DVSK(αMePhe)LDSRAA (O2Oc) 6αMePhe, K(O2Oc-O2Oc-γE-γE- (O2Oc) 10V, C20diacid)20D(αMePhe) 13αMePhe, VE(Aib)IANT-amide 18A, 20K, 22αMePhe, 24E, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 238 C20diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 234 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE-γE- (O2Oc) 10V, C20diacid)20DFVQ(Aib) 13αMePhe, IANTG-amide 18A, 20K, 25Aib, 26I, 27A, 30G Peptide H(Aib)HGS(αMePhe)TS 239 C20diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 235 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE-γE- (O2Oc) 10V, C20diacid)20DFVQ(Aib) 13αMePhe, IANTGG-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A, 30G, 31G Peptide H(Aib)HGS(αMePhe)TS 240 C18diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 236 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE-γE- (O2Oc) 10V, C18diacid)20DFVQ(Aib) 13αMePhe, IANTG-amide 18A, 20K, 25Aib, 26I, 27A, 30G Peptide H(Aib)HGS(αMePhe)TS 241 C18diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 237 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE-γE- (O2Oc) 10V, C18diacid)20DFVQ(Aib) 13αMePhe, IANTGG-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A, 30G, 31G Peptide H(Aib)HGS(αMePhe)TS 242 C20diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 238 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE-γE- (O2Oc) 10V C20diacid)20D(αMePhe) 13αMePhe, VQWIANTG-amide 18A, 20K, 22αMePhe, 26I, 27A, 30G Peptide H(Aib)HGS(αMePhe)TS 243 C20diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 239 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE-γE- (O2Oc) 10V, C20diacid)20D(αMePhe) 13αMePhe, VQWIANTGG-amide 18A, 20K, 22αMePhe, 26I, 27A, 30G, 31G Peptide H(Aib)HGS(αMePhe)TS 244 C18diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 240 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE-γE- (O2Oc) 10V, C18diacid)20D(αMePhe) 13αMePhe, VQWIANTG-amide 18A, 20K, 22αMePhe, 26I, 27A, 30G Peptide H(Aib)HGS(αMePhe)TS 245 C18diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 241 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE-γE- (O2Oc) 10V, C18diacid)20D(αMePhe) 13αMePhe, VQWIANTGG-amide 18A, 20K, 22αMePhe, 26I, 27A, 30G, 31G Peptide H(Aib)HGS(αMePhe)TS 246 C20diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 242 DVSK(αMePhe)LDSR (O2Oc)- 6αMePhe, (Aib)AK(O2Oc-O2Oc-γE- (O2Oc) 10V, γE- 13αMePhe, C20diacid)20DFVQSIAN 18Aib, 20K, T-amide 25S, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 247 C18diacid γE- 20 Amide 2Aib, 3H, 5S, 243 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)20D(αMePhe) 13αMePhe, VQSIANT-amide 18A, 20K, 22αMePhe, 25S, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 248 C20diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 244 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE-γE- (O2Oc) 10V, C20diacid)20D(αMePh 13αMePhe, e)VQSIANT-amide 18A, 20K, 22αMePhe, 25S, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 249 C18diacid γE- 20 Amide 2Aib, 3H, 5S, 245 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)20D(αMePhe) 13αMePhe, VESIANT-amide 18A, 20K, 22αMePhe, 24E, 25S, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 250 C20diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 246 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE-γE- (O2Oc) 10V, C20diacid)20D(αMePhe) 13αMePhe, VESIANT-amide 18A, 20K, 22αMePhe, 24E, 25S, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 251 C18diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 247 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE-γE- (O2Oc) 10V, C18diacid)20D(αMePhe) 13αMePhe, VQWIANT-amide 18A, 20K, 22αMePhe, 26I, 27A Peptide (NHis)SHGS(αMePhe)T 252 C20diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 248 SDVSK(αMePhe)LDSRA (O2Oc)- 6αMePhe, AK(O2Oc-O2Oc-γE-γE- (O2Oc) 10V, C20diacid)20D(αMePhe) 13αMePhe, VQWIANT-amide 18A, 20K, 22αMePhe, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 253 C20diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 249 DVSK(αMePhe)LDSR (O2Oc)- 6αMePhe, (Aib)AK(O2Oc-O2Oc-γE- (O2Oc) 10V, γE- 13αMePhe, C20diacid)20D(αMePhe) 18Aib, 20K, VESIANT-amide 22αMePhe, 24E, 25S, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 254 C18diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 250 DVSK(αMePhe)LDSR (O2Oc)- 6αMePhe, (Aib)AK(O2Oc-O2Oc-γE- (O2Oc) 10V, γE- 13αMePhe, C18diacid)20D(αMePhe) 18Aib, 20K, VESIANT-amide 22αMePhe, 24E, 25S, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 255 C18diacid γE- 20 Amide 2Aib, 3H, 5S, 251 DVSK(αMePhe)LDSR (O2Oc)- 6αMePhe, (Aib)AK(O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)20DFVESIAN 13αMePhe, T-amide 18Aib, 20K, 24E, 25S, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 256 C20diacid γE- 20 Amide 2Aib, 3H, 5S, 252 DVSK(αMePhe)LDSR (O2Oc)- 6αMePhe, (Aib)AK(O2Oc-O2Oc-γE- (O2Oc) 10V, C20diacid)20DFVESIAN 13αMePhe, T-amide 18Aib, 20K, 24E, 25S, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 257 C18diacid γE- 20 Amide 2Aib, 3H, 5S, 253 DVSK(αMePhe)LDSR (O2Oc) 6αMePhe, (Aib)AK(O2Oc-γE- 10V, C18diacid)20DFVESIAN 13αMePhe, T-amide 18Aib, 20K, 24E, 25S, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 258 C18diacid YE 20 Amide 2Aib, 3H, 5S, 254 DVSK(αMePhe)LDSR 6αMePhe, (Aib)AK(γE- 10V, C18diacid)20DFVESIAN 13αMePhe, T-amide 18Aib, 20K, 24E, 25S, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 259 C18diacid γE- 20 Amide 2Aib, 3H, 5S, 255 DVSK(αMePhe)LDSQAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 17Q, 18A, 20K 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 260 C20diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 256 DVSK(αMePhe)LDSQAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE-γE- (O2Oc) 10V C20diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 17Q,18A, 20K 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 261 Stearoyl γE-γE- 20 Amide 2Aib, 3H, 5S, 257 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE-γE- (O2Oc) 10V, Stearoyl)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 262 C18diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 258 DVSK(αMePhe)LDSRAA (PEG)2- 6αMePhe, K((PEG)2-(PEG)2-γE-γE- (PEG)2 10V, C18diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 263 C18diacid (O2Oc)- 20 Amide 2Aib, 3H, 5S, 259 DVSK(αMePhe)LDSRAA γE- 6αMePhe, K(O2Oc-γE-O2Oc- (O2Oc) 10V, C18diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 264 C18diacid γE- 20 Amide 2Aib, 3H, 5S, 260 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-γE-O2Oc-γE- γE- 10V, C18diacid)20D(αMePhe) (O2Oc) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 265 C18diacid γE- 20 Amide 2Aib, 3H, 5S, 261 DVSK(αMePhe)LDSRAA (PEG)4 6αMePhe, K((PEG)4-γE- 10V, C18diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 266 C18diacid γE- 20 Amide 2Aib, 3H, 5S, 262 DVSK(αMePhe)LDSRAA (O2Oc) 6αMePhe, K(O2Oc-γE- 10V, C18diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 267 C18diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 263 DVSK(αMePhe)LDSRAA (PEG)4 6αMePhe, K((PEG)4-γE-γE- 10V, C18diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 268 C20diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 264 DVSK(αMePhe)LDSRAA (PEG)2- 6αMePhe, K((PEG)2-(PEG)2-γE-γE- (PEG)2 10V, C20diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 269 C20diacid (O2Oc)- 20 Amide 2Aib, 3H, 5S, 265 DVSK(αMePhe)LDSRAA γE- 6αMePhe, K(O2Oc-γE-O2Oc- (O2Oc) 10V, C20diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 270 C20diacid γE- 20 Amide 2Aib, 3H, 5S, 266 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-γE-O2Oc-γE- γE- 10V, C20diacid)20D(αMePhe) (O2Oc) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 271 C20diacid γE- 20 Amide 2Aib, 3H, 5S, 267 DVSK(αMePhe)LDSRAA (PEG)4 6αMePhe, K(PEG)4-γE- 10V, C20diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 272 C20diacid γE- 20 Amide 2Aib, 3H, 5S, 268 DVSK(αMePhe)LDSRAA (O2Oc) 6αMePhe, K(O2Oc-γE- 10V, C20diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 273 C20diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 269 DVSK(αMePhe)LDSRAA (PEG)4 6αMePhe, K((PEG)4-γE-γE- 10V, C20diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 274 C18diacid γE-γE 20 Amide 2Aib, 3H, 5S, 270 DVSK(αMePhe)LDSRAA 6αMePhe, K(γE-γE- 10V, C18diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 275 C18diacid γE 20 Amide 2Aib, 3H, 5S, 271 DVSK(αMePhe)LDSRAA 6αMePhe, K(γE- 10V, C18diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 276 C18diacid (O2Oc)- 20 Amide 2Aib, 3H, 5S, 272 DVSK(αMePhe)LDSRAA (O2Oc) 6αMePhe, K(O2Oc-O2Oc- 10V, C18diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 277 C18diacid (O2Oc) 20 Amide 2Aib, 3H, 5S, 273 DVSK(αMePhe)LDSRAA 6αMePhe, K(O2Oc- 10V, C18diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 278 C18diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 274 DVSK(αMePhe)LDSRAA (O2Oc) 6αMePhe, K(O2Oc-γE-γE- 10V, C18diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 279 C20diacid γE-γE 20 Amide 2Aib, 3H, 5S, 275 DVSK(αMePhe)LDSRAA 6αMePhe, K(γE-γE- 10V, C20diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 280 C20diacid γE 20 Amide 2Aib, 3H, 5S, 276 DVSK(αMePhe)LDSRAA 6αMePhe, K(γE- 10V, C20diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 281 C20diacid (O2Oc)- 20 Amide 2Aib, 3H, 5S, 277 DVSK(αMePhe)LDSRAA (O2Oc) 6αMePhe, K(O2Oc-O2Oc- 10V, C20diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 282 C20diacid (O2Oc) 20 Amide 2Aib, 3H, 5S, 278 DVSK(αMePhe)LDSRAA 6αMePhe, K(O2Oc- 10V, C20diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 283 C20diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 279 DVSK(αMePhe)LDSRAA (O2Oc) 6αMePhe, K(O2Oc-γE-γE- 10V, C20diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 284 C20diacid γE- 20 Amide 2Aib, 3H, 5S, 280 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE- (O2Oc) 10V, C20diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide HSHGS(αMePhe)TSDVS 285 C20diacid γE-γE- 20 Amide 3H, 5S, 281 K(αMePhe)LDSRAAK (O2Oc)- 6αMePhe, (O2Oc-O2Oc-γE-γE- (O2Oc) 10V, C20diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGSFTSDVSK 286 C20diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 282 (αMePhe)LDSRAAK(O2Oc- (O2Oc)- 10V, O2Oc-γE-γE- (O2Oc) 13αMePhe, C20diacid)20D(αMePhe) 18A, 20K, VQ(Aib)IANT-amide 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 287 C20diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 283 DVSKYLDSRAAK(O2Oc- (O2Oc)- 6αMePhe, O2Oc-γE-γE- (O2Oc) 10V, 18A, C20diacid)20D(αMePhe) 20K, VQ(Aib)IANT-amide 22αMePhe, 25Aib, 26I, 27A Peptide HSHGS(αMePhe)TSDVS 288 C18diacid γE- 20 Amide 3H, 5S, 284 K(αMePhe)LDSRAAK (O2Oc)- 6αMePhe, (O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGSFTSDVSK(QM 289 C18diacid γE- 20 Amide 2Aib, 3H, 5S, 285 ePhe)LDSRAAK(O2Oc- (O2Oc)- 10V, O2Oc-γE- (O2Oc) 13αMePhe, C18diacid)20D(αMePhe) 18A, 20K, VQ(Aib)IANT-amide 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 290 C18diacid γE- 20 Amide 2Aib, 3H, 5S, 286 DVSKYLDSRAAK(O2Oc- (O2Oc)- 6αMePhe, O2Oc-γE- (O2Oc) 10V, 18A, C18diacid)20D(αMePhe) 20K, VQ(Aib)IANT-amide 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 291 C18diacid γE- 20 Amide 2Aib, 3H, 5S, 287 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)20DFVQ(Aib) 13αMePhe, IANT-amide 18A, 20K, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 292 C18diacid γE- 20 Amide 2Aib, 3H, 5S, 288 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)20D(αMePhe) 13αMePhe, VQWIANT-amide 18A, 20K, 22αMePhe, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 293 C20diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 289 DVSKYLDSRAAK(O2Oc- (O2Oc)- 6αMePhe, O2Oc-γE-γE- (O2Oc) 10v, 18A, C20diacid)20DFVQWIA 20K, 26I, 27A NT-amide Peptide H(Aib)HGSFTSDVSK 294 C20diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 290 (αMePhe)LDSRAAK(O2Oc- (O2Oc)- 10V, O2Oc-γE-γE- (O2Oc) 13αMePhe, C20diacid)20DFVQWIA 18A, 20K, NT-amide 26I, 27A Peptide H(Aib)HGSFTSDVSKYLD 295 C20diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 291 SRAAK(O2Oc-02Oc-γE- (O2Oc)- 10V, 18A, γE- (O2Oc) 20K, C20diacid)20D(αMePhe) 22αMePhe, VQWIANT-amide 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 296 C18diacid γE- 20 Amide 2Aib, 3H, 5S, 292 DVSKYLDSRAAK(O2Oc- (O2Oc)- 6αMePhe, O2Oc-γE- (O2Oc) 10V, 18A, C18diacid)20DFVQWIA 20K, 26I, 27A NT-amide Peptide H(Aib)HGSFTSDVSK 297 C18diacid γE- 20 Amide 2Aib, 3H, 5S, 293 (αMePhe)LDSRAAK(O2Oc- (O2Oc)- 10V, O2Oc-γE- (O2Oc) 13αMePhe, C18diacid)20DFVQWIA 18A, 20K, NT-amide 26I, 27A Peptide H(Aib)HGSFTSDVSKYLD 298 C18diacid γE- 20 Amide 2Aib, 3H, 5S, 294 SRAAK(O2Oc-O2Oc-γE- (O2Oc)- 10V, 18A, C18diacid)20D(αMePhe) (O2Oc) 20K, VQWIANT-amide 22αMePhe, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 299 C20diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 295 DVSK(AIb)LDSRAAK (O2Oc)- 6αMePhe, (O2Oc-O2Oc-γE-γE- (O2Oc) 10V, 13Aib, C20diacid)20D(αMePhe) 18A, 20K, VQ(Aib)IANT-amide 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 300 C18diacid γE- 20 Amide 2Aib, 3H, 5S, 296 DVSK(Aib)LDSRAAK (O2Oc)- 6αMePhe, (O2Oc-O2Oc-γE- (O2Oc) 10V, 13Aib, C18diacid)20D(αMePhe) 18A, 20K, VQ(Aib)IANT-amide 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 301 C18diacid γE- 20 Amide 2Aib, 3H, 5S, 297 DVSR(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE- (O2Oc) 10V, 12R, C18diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 302 C20diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 298 DVSR(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE-γE- (O2Oc) 10V, 12R, C20diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 303 C20diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 299 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE-γE- (O2Oc) 10V, C20diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IAET-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A, 28E Peptide H(Aib)HGS(αMePhe)TS 304 C18diacid γE- 20 Amide 2Aib, 3H, 5S, 300 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IAET-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A, 28E Peptide H(Aib)HGS(αMePhe)TS 305 C18diacid γE- 20 Amide 2Aib, 3H, 5S, 301 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)20D(αMePhe) 13αMePhe, IA(Aib)IAET-amide 18A, 20K, 22αMePhe, 231, 24A, 25Aib, 26I, 27A, 28E Peptide H(Aib)HGS(αMePhe)TS 306 C20diacid γE-γE- 20 Amide 2Aib, 3H, 5S, 302 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE-γE- (O2Oc) 10V, C20diacid)20D(αMePhe) 13αMePhe, IA(Aib)IAET-amide 18A, 20K, 22αMePhe, 231, 24A, 25Aib, 26I, 27A, 28E Peptide H(Aib)HGS(αMePhe)TS 307 C18diacid γE- 20 Acid 2Aib, 3H, 5S, 303 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-acid 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 308 C20diacid γE-γE- 20 Acid 2Aib, 3H, 5S, 304 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE-γE- (O2Oc) 10V, C20diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-acid 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGTFTSDVSK 309 C20diacid γE-γE- 20 Amide 2Aib, 3H, 305 (αMePhe)LDSRAAK(O2Oc- (O2Oc)- 10V, O2Oc-γE-γE- (O2Oc) 13αMePhe, C20diacid)20DFVQWIA 18A, 20K, NT-amide 26I, 27A Peptide H(Aib)QGTFTSDVSK 310 C18diacid γE- 20 Amide 2Aib, 10V, 306 (αMePhe)LDSRAAK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 18A, 20K, C18diacid)20DFVEWIA 24E, 26I, 27A NT-amide Peptide H(Aib)QGTFTSDVSK 311 C18diacid γE- 20 Amide 2Aib, 10V, 307 (αMePhe)LDSRAAK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 18A, 20K, C18diacid)20DFVRWIA 24R, 26I, NT-amide 27A Peptide H(Aib)QGTFTSDVSK 312 C18diacid γE- 20 Amide 2Aib, 10V, 308 (αMePhe)LDTRAAK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 16T, 18A, C18diacid)20DFVQWIA 20K, 26I, 27A NT-amide Peptide H(Ab)QGTFTSDVSK 313 C18diacid γE- 20 Amide 2Aib, 10V, 309 (αMePhe)LDERAAK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 16E, 18A, C18diacid)20DFVQWIA 20K, 26I, 27A NT-amide Peptide H(Aib)QGTFTSDVSK 314 C18diacid γE- 20 Amide 2Aib, 10V, 310 (αMePhe)LDSRAAK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 18A, 20K, C18diacid)20DFVQWLE 27E, 28A, AGG-amide 29G, 30G Peptide H(Aib)QGTFTSDVSK 315 C18diacid γE- 20 Amide 2Aib, 10V, 311 (αMePhe)LDSRAAK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 18A, 20K, C18diacid)20DFVQWLV 27V, 28E ET-amide Peptide H(Aib)QGTFTSDYSK 316 C18diacid γE- 20 Amide 2Aib, 10V, 312 (αMePhe)LDSRRAK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 18A, 20K, C18diacid)20DFVQWLV 27V, ((PEG)4)-amide 28(PEG)4, des29 Peptide H(Aib)QGTFTSDVSK 317 C18diacid γE- 20 Acid 2Aib, 10V, 313 (αMePhe)LDSR(Aib)AK (O2Oc)- 13αMePhe, (O2Oc-O2Oc-γE- (O2Oc) 18Aib, 20K, C18diacid)20DFVQWLL 27L NT-acid Peptide H(Aib)QGTFTSDVSK 318 C18diacid γE- 20 Amide 2Aib, 10V, 314 (αMePhe)LDSR(Aib)AK (O2Oc)- 13αMePhe, (O2Oc-O2Oc-γE- (O2Oc) 18Aib, 20K, C18diacid)20DFVQ(Aib) 25Aib, 27V, LVAT-amide 28A Peptide H(Aib)QGTFTSDVSK 319 C18diacid γE- 20 Amide 2Aib, 10V, 315 (αMePhe)LDSRAAK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 18A, 20K, C18diacid)20DFVQ(Aib) 25Aib, 27V, LVAT-amide 28A Peptide HSQGTFTSDYSK(αMePhe) 320 C18diacid γE- 20 Amide 13αMeF, 316 LEEEAVK(O2Oc- (O2Oc)- 15E, 16E, O2Oc-γE- (O2Oc) 17E, 18A, stearOOH)20LFIRWLM 19V, 20K, NT-amide 21L, 23I, 24R Peptide H(Aib)OGTFTSDVSK 321 C18diacid γE- 20 Amide 2Aib, 10V, 317 (αMePhe)LD(Aib)RAAK (O2Oc)- 13αMePhe, (O2Oc-O2Oc-γE- (O2Oc) 16Aib, 18A, C18diacid)20DFVQWIA 20K, 25Aib, NT-amide 26I, 27A Peptide H(αMeSer)QGTFTSDVS 322 C18diacid γE- 20 Amide 2αMeSer, 318 K(αMePhe)LDSRAAK (O2Oc)- 10V, (O2Oc-O2Oc-γE- (O2Oc) 13αMePhe, C18diacid)20DFVQWIA 18A, 20K, NT-amide 26I, 27A Peptide HS(αMeGln)GTFTSDVS 323 C18diacid γE- 20 Amide 3αMeGln, 319 K(αMePhe)LDSRAAK (O2Oc)- 10V (O2Oc-O2Oc-γE- (O2Oc) 13αMePhe, C18diacid)20DFVQWIA 18A, 20K, NT-amide 26I, 27A Peptide H(DSer)QGTFTSDVSK 324 C18diacid γE- 20 Amide 2ds, 10V, 320 (αMePhe)LDSRAAK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 18A, 20K, C18diacid)20DFVQWIA 26I, 27A NT-amide Peptide H(Aib)QGS(αMePhe)TS 325 C18diacid γE- 20 Amide 2Aib, 5S, 321 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)QGS(αMePhe)TS 326 C20diacid γE- 20 Amide 2Aib, 5S, 322 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, K(O2Oc-O2Oc-γE-γE- (O2Oc) 10V, C20diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide HS(αMeGln)GS(αMePhe) 327 C18diacid γE- 20 Amide 3αMeGln, 323 TSDVSK(αMePhe)LDS (O2Oc)- 5S, RAAK(O2Oc-O2Oc-γE- (O2Oc) 6αMePhe, C18diacid)20D(αMePhe) 10V, VQ(Aib)IANT-amide 13αMePhe, 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide HS(ß- 328 C18diacid γE- 20 Amide 3ß- 324 dimethylGln)GS(αMePhe) (O2Oc)- dimethylGln, TSDVSK(αMePhe)LD (O2Oc) 5S, SRAAK(O2Oc-O2Oc-γE- 6αMePhe, C18diacid)20D(αMePhe) 10V, VQ(Aib)IANT-amide 13αMePhe, 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide HS(N- 329 C18diacid γE- 20 Amide 3N-MeGln, 325 MeGln)GS(αMePhe)TS (O2Oc)- 55, DVSK(αMePhe)LDSRAA (O2Oc) 6αMePhe, K(O2Oc-O2Oc-γE- 10V, C18diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide HS(dGln)GS(αMePhe)T 330 C18diacid γE- 20 Amide 3dGln, 5S, 326 SDVSK(αMePhe)LDSRA (O2Oc)- 6αMePhe, AK(O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Acpr)QGS(αMePhe)T 331 C18diacid γE- 20 Amide 2Acpr, 5S, 327 SDVSK(αMePhe)LDSRA (O2Oc)- 6αMePhe, AK(O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Acbu)QGS(αMePhe) 332 C18diacid γE- 20 Amide 2Acbu, 5S, 328 TSDVSK(αMePhe)LDSR (O2Oc)- 6αMePhe, AAK(O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(αMeSer)QGS(αMePhe) 333 C18diacid γE- 20 Amide 2αMeSer, 329 TSDVSK(αMePhe)LDS (O2Oc)- 5S, RAAK(O2Oc-O2Oc-γE- (O2Oc) 6αMePhe, C18diacid)20D(αMePhe) 10V, VQ(Aib)IANT-amide 13αMePhe, 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(dSer)QGS(αMePhe)T 334 C18diacid γE- 20 Amide 2dSer, 5S, 330 SDVSK(αMePhe)LDSRA (O2Oc)- 6αMePhe, AK(O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)20D(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 20K, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)QGTFTSDVSK 335 C18diacid γE- 20 Acid 2Aib, 10V, 331 (αMePhe)LDSRRAK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 20K, 24R, C18diacid)20DFVRWLL 27L, 28E, E(Aib)G-acid 29Aib, 30G Peptide H(Aib)QGTFTSDVSK 336 C18diacid γE- 20 Acid 2Aib, 10V, 332 (αMePhe)LDSRRAK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 20K, 27L, C18diacid)20DFVQWLL 28E, 29Aib, E(Aib)G-acid 30G Peptide H(Aib)QGTFTSDVSK 337 C18diacid γE- 20 Acid 2Aib, 10V, 333 (αMePhe)LDSRRAK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 20K, 27L, C18diacid)20DFVQWLL 28Aib, 30E (Aib)TE-acid Peptide H(Aib)QGTFTSDYSK 338 C18diacid γE 20 Acid 2Aib, 334 (αMePhe)LDSRRAK(γE- 13αMePhe, C18diacid)20DFVQWLA 20K, 27A, (Aib)E-acid 28Aib, 30E Peptide H(Ab)QGTFTSDYSK 339 C18diacid γE 20 Acid 2Aib, 335 (αMePhe)LDSRRAK(γE- 13αMePhe, C18diacid)20DFVQWLL 20K, 27L, E(Aib)G-acid 28E, 29Aib, 30G Peptide H(Ab)QGTFTSDYSK 340 C18diacid γE 20 Acid 2Aib, 336 (αMePhe)LDSRRAK(γE- 13αMePhe, C18diacid)20DFVQWLIS 20K, 27I, E-acid 28S, 29E Peptide H(Aib)QGTFTSDYSK 341 C18diacid γE 20 Acid 2Aib, 337 (αMePhe)LDSRRAK(γE- 13αMePhe, C18diacid)20DFVQWLL 20K, 27L, (Aib)T-acid 28Aib Peptide H(Aib)QGTFTSDYSK 342 C18diacid γE 20 Acid 2Aib, 338 (αMePhe)LD(Aib)RRAK 13αMePhe, (γE-C18diacid)20DFVQW 16Aib, 20K, LL(Aib)T-acid 27L, 28Aib Peptide H(Aib)QGTFTSDYSK 343 C18diacid γE 20 Acid 2Aib, 339 (αMePhe)LDSRRAK(γE- 13αMePhe, C18diacid)20DFVQWLL 20K, 27L, (Aib)E-acid 28Aib, 29E Peptide H(Aib)QGTFTSDYSK 344 C18diacid γE 20 Acid 2Aib, 340 (αMePhe)LDSRRAK(γE- 13αMePhe, C18diacid)20DFVQWLL 20K, 27L, (Aib)TE-acid 28Aib, 30E Peptide H(Aib)QGTFTSDYSK 345 C18diacid γE 20 Acid 2Aib, 341 (αMePhe)LDSRRAK(γE- 13αMePhe, C18diacid)20DFVQWLL 20K, 27L E(Aib)T-acid 28E, 29Aib, 30T Peptide H(Aib)QGTFTSDVSK 346 C18diacid γE 20 Acid 2Aib, 10V, 342 (αMePhe)LDSRAAK(γE- 13αMePhe, C18diacid)20DFVQWIA 18A, 20K, NT-acid 26I, 27A Peptide H(Aib)QGTFTSDVSK 347 C18diacid γE- 20 Amide 2Aib, 10V, 343 (αMePhe)LDSRAAK(γE-γE- γE(O2Oc 13αMePhe, O2Oc-O2Oc-γE-γE- 1- 18A, 20K, C18diacid)20DFVQWIA (O2Oc)- 26I, 27A NT-amide γE-γE Peptide H(Aib)QGTFTSDVSK 532 C18diacid γE- 20 Acid 2Aib, 10V, 521 (αMePhe)LDSERAK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17E, 20K, C18diacid)20DFVQWLE 27E, 28A, AGG-acid 29G, 30G Peptide H(Aib)QGTFTSDVSK 533 C18diacid γE- 20 Acid 2Aib, 10V, 522 (αMePhe)LDSERAK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17E, 20K, C18diacid)20DFVAWLE 24A, 27E, AGG-acid 28A, 29G, 30G Peptide H(Ab)QGTFTSDVSK 534 C20diacid γE- 20 Acid 2Aib, 10V, 523 (αMePhe)LDSERAK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17E, 20K, C20diacid)20DFVAWLE 24A, 27E, AGG-acid 28A, 29G, 30G Peptide H(Aib)QGTFTSDVSE 535 C18diacid γE- 20 Acio 2Aib, 10V, 524 (αMePhe)LDSERAK(O2Oc- (O2Oc)- 12E O2Oc-γE- (O2Oc) 13αMePhe, C18diacid)20DFVRWLE 17E, 20K, AGG-acid 24R, 27E, 28A, 29G, 30G Peptide H(Aib)QGTFTSDVSK 536 C18diacid γE- 20 Acid 2Aib, 10V, 525 (αMePhe)LDSERAK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17E, 20K, C18diacid)20DFVQWLE 27E, 28A, A(Aib)G-acid 29Aib, 30G Peptide H(Aib)QGTFTSDVSK 537 C18diacid γE- 20 Acid 2Aib, 10V, 526 (αMePhe)LDSERAK(O2Oc- (O2Oc)- 13αMePhe, O2Oc-γE- (O2Oc) 17E, 20K, C18diacid)20DFVAWLE 24A, 27E, A(Aib)G-acid 28A, 29Aib, 30G

In some aspects, the peptide comprises the sequence: X1-X2-X3-G-X5-X6-T-S-D-X10-S-K-X13-L-X15-X16-X17-X18-X19-X20-X21-X22-X23-X24-X25-X26-X27-X28-X29-X30-X31-Z, wherein X1 is H or ((1H-imidazol-4-yl)methyl)glycine (NHis), X2 is S or Aminoisobutyric acid (Aib), X3 is Q, H, or I, X5 is T or S, X6 is F or αMethyl-Phenylalanine (αMePhe), X10 is Y or V, X13 is Y, αMePhe, Aib, or Diphenylalanine (Dip), X15 is D or E, X16 is S, E, or L, X17 is R, Q, or E, X18 is R, A, or Aib, X19 is A or V, X20 is Q or R, X21 is D or L, X22 is F or αMePhe, X23 is V or I, X24 is Q or K, wherein the K can comprise an acyl moiety and/or can be lipidated, X25 is W, Aib, or S, X26 is L or I, X27 is M, V, L, or A, X28 is N, E, or Aib, X29 is T, Aib, G, or not present, X30 is not present, Aib, or G, X31 is not present or G, and Z is amide or acid (SEQ ID NO: 415), wherein the peptide does not comprise SEQ ID NO: 1.

In some aspects, the residue at position 24 is acylated. In some aspects, the residue at position 24 is lipidated. In some aspects, the lipid is selected from the group consisting of a palmitoyl group, stearoyl group, lauryl group, myristoyl group, margaroyl group, octadecanedioic acid (C18diacid), and icosanedioic acid (C20diacid). In some aspects, the lipid is selected from the group consisting of an octadecanedioic acid (C18diacid), and icosanedioic acid (C20diacid).

In some aspects, the lipid attached to the residue at position 24 is attached via a linker. In some aspects, the linker is selected from the group consisting of (O2Oc), (O2Oc)-(O2Oc), (O2Oc)-γE-(O2Oc), (PEG)2-(PEG)2-γE-γE, (PEG)2-γE-(PEG)2-γE, γE, γE-(O2Oc), γE-(O2Oc)-(O2Oc), γE-(O2Oc)-γE-(O2Oc), γE-(PEG)2-(PEG)2, γE-(PEG)2-γE-(PEG)2, γE-(PEG)4, γE-γE, γE-γE-(O2Oc), γE-γE-(O2Oc)-(O2Oc), γE-γE-(PEG)12, γE-γE-(PEG)2-(PEG)2, γE-γE-(PEG)2-γE-γE, γE-γE-(PEG)4, and γE-γE-(PEG)8. In some aspects, linker is selected from the group consisting of γE, γE-(O2Oc)-(O2Oc), γE-γE-(PEG)2-(PEG)2, γE-γE-(PEG)2-γE-γE, and γE-γE-(O2Oc)-(O2Oc).

In some aspects, the peptide comprises the sequence: H-Aminoisobutyric acid (Aib)-Q-G-T-F-T-S-D-V-S-K-αMethyl-Phenylalanine (αMePhe)-L-X15-X16-R-R-A-Q-D-F-V-K-W-L-X27-X28-X29-X30-Z, wherein X15 is D or E, X16 is S or L, X27 is V or L, X28 is E or Aib, X29 is T, Aib or G, X30 is G or Aib or not present, Z is amide or acid (SEQ ID NO: 416).

In some aspects, the lysine at position 24 is acylated. In some aspects, the lipid is selected from the group consisting of a palmitoyl group, stearoyl group, lauryl group, myristoyl group, margaroyl group, octadecanedioic acid (C18diacid), and icosanedioic acid (C20diacid). In some aspects, the lysine at position 24 is lipidated. In some aspects, the lipid is octadecanedioic acid (C18diacid).

In some aspects, the lipid is linked to the lysine at position 24 via a linker. In some aspects, the linker is selected from the group consisting of (O2Oc), (O2Oc)-(O2Oc), (O2Oc)-γE-(O2Oc), (PEG)2-(PEG)2-γE-γE, (PEG)2-γE-(PEG)2-γE, γE, γE-(O2Oc), γE-(O2Oc)-(O2Oc), γE-(O2Oc)-γE-(O2Oc), γE-(PEG)2-(PEG)2, γE-(PEG)21γE-(PEG)2, γE-(PEG)4, γE-γE, γE-γE-(O2Oc), γE-γE-(O2Oc)-(O2Oc), γE-γE-(PEG)12, γE-γE-(PEG)2-(PEG)2, γE-γE-(PEG)2-γE-γE, γE-γE-(PEG)4, and γE-γE-(PEG)8. In some aspects, the linker is γE-(O2Oc)-(O2Oc).

In certain aspects, GLP-1/glucagon agonist peptides as disclosed have desirable potencies at the glucagon and GLP-1 receptors.

In some aspects, the peptide comprises any one of SEQ ID NOs: 348-395.

In some aspects, the peptide is any one any of the peptides in Table 3.

TABLE 3 Peptides Modified at Position 24 Linker Sequence Albumin (described Acyl- modification binding N→C ation C- with respect Peptide Sequence moiety term) site term. to glucagon Peptide H(Aib)QGSFTSDVSK(Dip) 348 C18diacid γE 24 Amide 2Aib, 5S, 10V, 343 LDSRAAQDFVK(γE- 13Dip, 18A, C18diacid)24WIANT- 24K, 26I, 27A amide Peptide HSQGS(αMePhe)TSDVS 349 C18diacid γE- 24 Amide 5S, 344 K(Aib)LDSRAAQD (O2Oc)- 6αMePhe, (αMePhe)VK(O20C-O20C- (O2Oc) 10V, 13Aib, γE- 18A, C18diacid)24(Aib)IAN- 22αMePhe, amide 24K, 25Aib, 26I, 27A, des29T Peptide H(Aib)HGTFTSDVSK 350 C18diacid γE 2.4 Amide 2Aib, 3H, 345 (αMePhe)LDSQAAQDFVK (O2Oc)- 10V, (O2Oc-O2Oc-γE- (O2Oc) 13αMePhe, C18diacid)24WIANT- 17Q,18A, amide 24K, 26I, 27A Peptide H(Aib)HGTFTSDVSK 351 C18diacid γE 24 Amide 2Aib, 3H, 346 (αMePhe)LDSQAAQDFVK 10V, (γE- 13αMePhe, C18diacid)24WIANT- 17Q,18A, amide 24K, 26I, 27A Peptide H(Aib)HGTFTSDVSK 352 C20diacid γE 24 Amide 2Aib, 3H, 347 (αMePhe)LDSQAAQDFVK 10V, (γE- 13αMePhe, C20diacid)24WIANT- 170, 18A, amide 24K, 26I, 27A Peptide H(Aib)QGS(αMePhe)TS 353 C18diacid γE- 24 Amide 2Aib, 5S, 348 DVSK(αMePhe)LDSQAA (O2Oc)- 6αMePhe, QDFVK(O2Oc-O20c-γE- (O2Oc) 10V, C18diacid)24WIANT- 13αMePhe, amide 17Q, 18A, 24K, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 354 C18diacid γE- 24 Amide 2Aib, 3H, 5S, 349 DVSK(αMePhe)LDSQAA (O2Oc)- 6αMePhe, QDFVK(O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)24WIANT- 13αMePhe, amide 17Q, 18A, 24K, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 355 C18diacid γE- 24 Amide 2Aib, 3H, 5S, 350 DVSK(αMePhe)LDSQAA (O2Oc)- 6αMePhe, QDFVK(O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)24WIANTGG 13αMePhe, -amide 17Q,18A, 24K, 261, 27A, 30G, 31G Peptide H(Aib)HGS(αMePhe)TS 356 C18diacid γE 24 Amide 2Aib, 3H, 5S, 351 DVSK(αMePhe)LDSQAA 6αMePhe, QDFVK(γE- 10V, C18diacid)24WIANT- 13αMePhe, amide 170,18A, 24K, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 357 C18diacid γE-γE- 24 Amide 2Aib, 3H, 5S, 352 DVSK(αMePhe)LDSQAA (PEG)2- 6αMePhe, QDFVK((PEG)2-(PEG)2- (PEG)2 10V, γE-γE- 13αMePhe, C18diacid)24WIANT- 170, 18A, amide 24K, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 358 C18diacid γE-γE- 24 Amide 2Aib, 3H, 5S, 353 DVSK(αMePhe)LDSQAA (PEG)2- 6αMePhe, QDFVK(YE-YE-(PEG)2- γE-γE 10V, γE-γE- 13αMePhe, C18diacid)24WIANT- 17Q, 18A, amide 24K, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 359 C20diacid γE 24 Amide 2Aib, 3H, 5S, 354 DVSK(αMePhe)LDSQAA 6αMePhe, QDFVK(γE- 10V, C20diacid)24WIANT- 13αMePhe, amide 170,18A, 24K, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 360 C20diacid γE-γE- 24 Amide 2Aib, 3H, 5S, 355 DVSK(αMePhe)LDSQAA (PEG)2- 6αMePhe, QDFVK((PEG)2-(PEG)2- (PEG)2 10V, γE-γE- 13αMePhe, C20diacid)24WIANT- 170, 18A, amide 24K, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 361 C20diacid γE- 24 Amide 2Aib, 3H, 5S, 356 DVSK(αMePhe)LDSQAA (O2Oc)- 6αMePhe, QDFVK(O2OC-O20C- (O2Oc) 10V, γE- 13αMePhe, C20diacid)24WIANT- 170, 18A, amide 24K, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 362 C20diacid γE-γE- 24 Amide 2Aib, 3H, 5S, 357 DVSK(αMePhe)LDSQAA (PEG)2- 6αMePhe, QDFVK(γE-γE-(PEG)2- γE-γE 10V, γE-γE- 13αMePhe, C20diacid)24WIANT- 17Q, 18A, amide 24K, 26I, 27A Peptide H(Aib)IGS(αMePhe)TSD 363 C18diacid γE- 24 Amide 2Aib, 3I, 5S, 358 VSK(αMePhe)LDSQAA (O2Oc)- 6αMePhe, QDFVK(O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)24WIANT- 13αMePhe, amide 17Q,18A, 24K, 26I, 27A Peptide H(Aib)IGS(αMePhe)TSD 364 C18diacid γE- 24 Amide 2Aib, 3I, 5S, 359 VSK(αMePhe)LDSRAAQ (O2Oc)- 6αMePhe, DFVK(O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)24WIANT- 13αMePhe, amide 18A, 24K, 26I, 27A Peptide H(Aib)IGS(αMePhe)TSD 365 C20diacid γE- 24 Amide 2Aib, 3I, 5S, 360 VSK(αMePhe)LDSRAAQ (O2Oc)- 6αMePhe, DFVK(O2OC-O2OC-γE- (O2Oc) 10V, C20diacid)24WIANT- 13αMePhe, amide 18A, 24K, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 366 C18diacid γE- 24 Amide 2Aib, 3H, 5S, 361 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, QDFVK(O2Oc-O2Oc-γE- (O2Oc) 10V C18diacid)24WIANT- 13αMePhe, amide 18A, 24K, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 367 C18diacid γE-γE- 24 Amide 2Aib, 3H, 5S, 362 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, QDFVK(O2OC-O2OC- (O2Oc) 10V, γE-γE- 13αMePhe, C18diacid)24WIANT- 18A, 24K, 26I, amide 27A Peptide H(Aib)HGS(αMePhe)TS 368 C18diacid γE-γE- 24 Amide 2Aib, 3H, 5S, 363 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, QDFVK(O2OC-O2OC- (O2Oc) 10V, γE-γE- 13αMePhe, C18diacid)24WIANTG- 18A, 24K, 26I, amide 27A, 30G Peptide H(Aib)HGS(αMePhe)TS 369 C18diacid γE-γE- 24 Amide 2Aib, 3H, 5S, 364 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, QDFVK(O2OC-O2OC- (O2Oc) 10V, γE-γE- 13αMePhe, C18diacid)24WIANTGG- 18A, 24K, 26I, amide 27A, 31G Peptide H(Aib)HGS(αMePhe)TS 370 C18diacid γE- 24 Amide 2Aib, 3H, 5S, 365 DVSK(αMePhe)LDSR(Aib) (O2Oc)- 6αMePhe, AQDFVK(O2Oc- (O2Oc) 10V, O2Oc-γE- 13αMePhe, C18diacid)24WIANT- 18Aib, 24K, amide 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 371 C18diacid γE- 24 Amide 2Aib, 3H, 5S, 366 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, QDFVK(O2Oc-O2Oc-γE- (O2Oc) 10V, C18diacid)24(Aib)IANT- 13αMePhe, amide 18A, 24K, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 372 C20diacid γE- 24 Amide 2Aib, 3H, 5S, 367 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, QDFVK(O2OC-O2OC- (O2Oc) 10V, γE- 13αMePhe, C20diacid)24WIANT- 18A, 24K, 26I, amide 27A Peptide H(Aib)HGS(αMePhe)TS 373 C20diacid γE- 24 Amide 2Aib, 3H, 5S, 368 DVSK(αMePhe)LDSR(Aib) (O2Oc)- 6αMePhe, AQDFVK(O2OC- (O2Oc) 10V, O2OC-γE- 13αMePhe, C20diacid)24WIANT- 18Aib, 24K, amide 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 374 C20diacid γE- 24 Amide 2Aib, 3H, 5S, 369 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, QDFVK(O2OC-O2OC- (O2Oc) 10V, γE- 13αMePhe, C20diacid)24(Aib)IANT- 18A, 24K, amide 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 375 C18diacid γE- 24 Amide 2Aib, 3H, 5S, 370 DVSK(αMePhe)LDSQAA (O2Oc)- 6αMePhe, QD(αMePhe)VK(O2Oc- (O2Oc) 10V, O20c-γE- 13αMePhe, C18diacid)24WIANT- 170,18A, amide 22αMePhe, 24K, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 376 C18diacid γE-γE- 24 Amide 2Aib, 3H, 5S, 371 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, QD(αMePhe)VK(O2OC₂- (O2Oc) 10V, γE-γE- 13αMePhe, C18diacid)24WIANT- 18A, amide 22αMePhe, 24K, 26I, 27A Peptide H(Ab)HGS(αMePhe)TS 377 C18diacid γE-γE- 24 Amide 2Aib, 3H, 5S, 372 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, QD(αMePhe)VK(O2OC₂- (O2Oc) 10V, γE-γE- 13QMePhe, C18diacid)24(Aib)IANT- 18A, amide 22αMePhe, 24K, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 378 C18diacid γE-γE- 24 Amide 2Aib, 3H, 5S, 373 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, QD(αMePhe)VK(O2OC₂- (O2Oc) 10V, γE-γE- 13αMePhe, C18diacid)24(Aib)IANT 18A, GG-amide 22αMePhe, 24K, 25Aib, 26I, 27A, 30G, 31G Peptide H(Aib)HGS(αMePhe)TS 379 C20diacid γE-γE- 24 Amide 2Aib, 3H, 5S, 374 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, QD(αMePhe)VK(O2OC₂- (O2Oc) 10V, γE-γE- 13αMePhe, C20diacid)24WIANT- 18A, amide 22αMePhe, 24K, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 380 C20diacid γE-γE- 24 Amide 2Aib, 3H, 5S, 375 DVSK(αMePhe)LDSRAA (O2Oc)- 60MePhe, QD(αMePhe)VK(O2OC₂- (O2Oc) 10V, γE-γE- 13αMePhe, C20diacid)24(Aib)IANT- 18A, amide 22αMePhe, 24K, 25Aib, 26I ,27A Peptide H(Aib)HGS(αMePhe)TS 381 C20diacid γE-γE- 24 Amide 2Aib, 3H, 5S, 376 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, QD(αMePhe)VK(O2OC₂- (020° C.) 10V, γE-γE- 13αMePhe, C20diacid)24(Aib)IANT 18A, GG-amide 22oMePhe, 24K, 25Aib, 261,27A, 30G, 31G Peptide H(Aib)HGS(αMePhe)TS 382 C20diacid γE-γE- 24 Amide 2Aib, 3H, 5S, 377 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, QDFVK(O2OC₂-γE-γE- (O2Oc) 10V, C20diacid)24WIANT- 13αMePhe, amide 18A, 24K, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 383 C18diacid γE-γE- 24 Amide 2Aib, 3H, 5S, 378 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, QD(αMePhe)VK(O2OC₂- (O2Oc) 10V, γE-γE- 13QMePhe, C18diacid)24SIANT- 18A, amide 22QMePhe, 24K, 25S, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 384 C18diacid γE-γE- 24 Amide 2Aib, 3H, 5S, 379 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, QD(αMePhe)VK(O2OC₂- (O2Oc) 10V, γE-C18diacid)24SIANT- 13αMePhe, amide 18A, 22αMePhe, 24K, 25S, 26I, 27A Peptide (NHis)SHGS(αMePhe)T 385 C20diacid γE-γE- 24 Amide 1NHis, 3H, 380 SDVSK(αMePhe)LDSRA (O2Oc)- 5S, AQDFVK(O2OC₂-γE-γE- (O2Oc) 6αMePhe, C20diacid)24WIANT- 10V, amide 13αMePhe, 18A, 24K, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 386 C18diacid γE-γE- 24 Amide 2Aib, 3H, 5S, 381 DVSK(αMePhe)LDSRAA (O2Oc)- 6αMePhe, QDFVK(O2OC-O2OC- (O2Oc) 10V, γE-γE- 13αMePhe, C18diacid)24SIANTGG- 18A, 24K, amide 25S, 26I, 27A, 30G, 31G Peptide H(Aib)HGS(αMePhe)TS 387 C18diacid γE-γE- 24 Amide 2Aib, 3H, 5S, 382 DVSK(αMePhe)LDSR (O2Oc)- 6αMePhe, (Aib)AQDFVK(O2OC- (O2Oc) 10V, O2OC-γE-γE- 13αMePhe, C18diacid)24SIANTGG- 18Aib, 24K, amide 25S, 26I, 27A, 30G, 31G Peptide H(Aib)HGS(αMePhe)TS 388 C18diacid γE- 24 Amide 2Aib, 3H, 5S, 383 DVSK(αMePhe)LDSQAA (O2Oc)- 6αMePhe, QD(αMePhe)VK(O2Oc- (O2Oc) 10V, O2Oc-γE- 13αMePhe, C18diacid)24(Aib)IANT- 17Q, 18A, amide 22αMePhe, 24K, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 389 C20diacid γE-γE- 24 Amide 2Aib, 3H, 5S, 384 DVSK(αMePhe)LDSQAA (O2Oc)- 6αMePhe, QD(αMePhe)VK(O2OC- (O2Oc) 10V, O2OC-γE-γE- 13QMePhe, C20diacid)24(Aib)IANT- 17Q, 18A, amide 22αMePhe, 24K, 25Aib, 26I, 27A Peptide HSQGTFTSDYSK(αMePhe) 390 C18diacid γE- 24 Amide 13αMePhe, 385 LEEEAVRLFIK(O2OC- (O2Oc)- 15E, 16E, O2OC-γE- (O2Oc) 17E, 18A, stearOOH)24WLMNT- 19V, 20R, amide 21L, 23I, 24K, Peptide H(Aib)QGTFTSDVSK 391 C18diacid γE- 24 Acid 2Aib, 10V, 386 (αMePhe)LDSRRAQDFVK (O2Oc)- 13αMePhe, (O2OC-O2OC-γE- (O2Oc) 24K, 25Aib, C18diacid)24WLVE(Aib) 27V, 28E, G-acid 29Aib, 30G Peptide H(Aib)QGTFTSDVSK 392 C18diacid γE- 24 Acid 2Aib, 10V, 387 (αMePhe)LESRRAQDFVK (O2Oc)- 13αMePhe, (O2OC-O2OC-γE- (O2Oc) 15E, 24K, C18diacid)24WLVE(Aib) 25Aib, 27V, G-acid 28E, 29Aib, 30G Peptide H(Aib)QGTFTSDVSK 393 C18diacid γE- 24 Acid 2Aib, 10V, 388 (αMePhe)LDLRRAQDFVK (O2Oc)- 13αMePhe, (O2OC-O2OC-γE- (O2Oc) 16L, 24K, C18diacid)24WLVE(Aib) 25Aib, 27V, G-acid 28E, 29Aib, 30G Peptide H(Aib)QGTFTSDVSK 394 C18diacid γE- 24 Acid 2Aib, 10V, 389 (αMePhe)LDSRRAQDFVK (O2Oc)- 13αMePhe, (O2OC-02OC-γE- (O2Oc) 24K, 25Aib, C18diacid)24WLL(Aib)T- 27L, 28Aib acid Peptide H(Aib)QGTFTSDVSK 395 C18diacid γE- 24 Acid 2Aib, 10V, 390 (αMePhe)LDSRRAQDFVK (O2Oc)- 13αMePhe, (O2OC-O2OC-γE- (O2Oc) 24K, 25Aib, C18diacid)24WLVEG 27V, 28E, (Aib)-acid 29G, 30Aib

In some aspects, the peptide comprises the sequence: H-X2-X3-G-X5-X6-T-S-D-X10-S-K-X13-L-D-S-X17-X18-A-Q-D-X22-V-X24-X25-X26-X27-N-T-X(30)-X(31)-Z, wherein X2 is S or Aminoisobutyric acid (Aib), X3 is Q or H, X5 is T or S, X6 is F or α-methylphenylalanine (αMePhe), X10 is Y, V, or K, wherein the K can comprise an acyl moiety and/or can be lipidated, X13 is Y, αMePhe, I, or Diphenylalanine (Dip), or K wherein the K can comprise an acyl moiety and/or can be lipidated, X17 is R, Q, or β-dimethylarganine (β-diMeArg), X18 is R or A, X22 is F or αMePhe, X24 is Q or E, X25 is W, Aib, or H, X26 is L or I, X27 is M or A, X(30) is not present, X(31) is not present, and Z is amide or acid (SEQ ID NO: 417), wherein the peptide does not comprise SEQ ID NO: 1.

In some aspects, the residue at position 10 or 13 is acylated. In some aspects, the residue at position 10 or 13 is lipidated. In some aspects, the lipid is selected from the group consisting of a palmitoyl group, stearoyl group, lauryl group, myristoyl group, margaroyl group, octadecanedioic acid (C18diacid), and icosanedioic acid (C20diacid). In some aspects, the lipid is selected from the group consisting of an octadecanedioic acid (C18diacid), and icosanedioic acid (C20diacid), stearoyl group, and palmitoyl group.

In some aspects, the lipid attached to the residue at position 10 or 13 is attached via a linker. In some aspects, the linker is selected from the group consisting of (O2Oc), (O2Oc)-(O2Oc), (O2Oc)-γE-(O2Oc), (PEG)2-(PEG)2-γE-γE, (PEG)2-γE-(PEG)2-γE, γE, γE-(O2Oc), γE-(O2Oc)-(O2Oc), γE-(O2Oc)-γE-(O2Oc), γE-(PEG)2-(PEG)2, γE-(PEG)2-γE-(PEG)2, γE-(PEG)4, γE-γE, γE-γE-(O2Oc), γE-γE-(O2Oc)-(O2Oc), γE-γE-(PEG)12, γE-γE-(PEG)2-(PEG)2, γE-γE-(PEG)2-γE-γE, γE-γE-(PEG)4, and γE-γE-(PEG)8. In some aspects, the linker is selected from the group consisting of γE-γE-(O2Oc)-(O2Oc), γE-(O2Oc)-(O2Oc), γE-γE-(PEG)2-(PEG)2, and γE-(PEG)2-(PEG)2.

In some aspects, the peptide comprises any one of SEQ ID NOs: 396-411.

In some aspects, the peptide is any one of the peptides in Table 4 or Table 5.

TABLE 4 Peptides Modified at Position 10 Sequence Albumin Linker Acyl- modification SEQ ID binding (described ation C- with respect Peptide Sequence NO moiety N→C) site term. to glucagon Peptide H(Aib)HGS(αMePhe)TS 396 C20diacid γE-γE- 10 Amide 2Aib, 3H, 5S, 390 DK(O2OC-O2OC-γE-γE- (O2Oc)- 6αMePhe, C20diacid)10SK(αMePhe) (O2Oc) 10K, LDSRAAQD(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 22αMePhe, 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 397 C18diacid γE- 10 Amide 2Aib, 3H, 5S, 391 DK(O2OC-O2OC-γE- (O2Oc)- 6αMePhe, C18diacid)10SK(αMePhe) (O2Oc) 10K, LDSRAAQD(αMePhe) 13αMePhe, VQ(Aib)IANT-amide 18A, 22αMePhe, 25Aib, 26I, 27A Peptide HSQGS(αMePhe)TSDK 398 Stearoyl γE-γE- 10 Amide 5S, 392 ((PEG)2-(PEG)2-γE-γE- (PEG)2- 6αMePhe, Stearoyl)10SK(Dip)LDS (PEG)2 10K, 13Dip, (ß- 17ß- dimethylArg)AAQD dimethylR, (αMePhe)VE(Aib)LANT- 18A, amide 22αMePhe, 24E, 25Aib, 27A Peptide HSQGS(αMePhe)TSDK 399 Palmitoyl γE-γE- 10 Amide 5S, 393 ((PEG)2-(PEG)2-γE-γE- (PEG)2- 6αMePhe, Palmitoyl)10SK(Dip)LDS (PEG)2 10K, 13Dip, (ß- 17ß- dimethylArg)AAQD dimethylR, (αMePhe)VE(Aib)LANT- 18A, amide 22αMePhe, 24E, 25Aib, 27A Peptide H(Aib)QGSFTSDK(PEG) 400 Palmitoyl γE- 10 Amide 2Aib, 5S, 394 2-(PEG)2-γE- (PEG)2- 10K, 13I, Palmitoyl)10SKILDSRAA (PEG)2 18A, 24E, QDEVEWIANT-amide 26I, 27A Peptide H(Aib)QGS(αMePhe)TS 401 Palmitoyl γE- 10 Amide 2Aib, 5S, 395 DK((PEG)2-(PEG)2-γE- (PEG)2- 6αMePhe, Palmitoyl)10SKILDSRAA (PEG)2 10K, 13I, QD(αMePhe)VEWIANT- 18A, amide 22αMePhe, 24E, 26I, 27A Peptide HSQGS(αMePhe)TSDK 402 Stearoyl γE-γE- 10 Amide 5S, 396 ((PEG)2-(PEG)2-γE-γE- (PEG)2- 6αMePhe, Stearoyl)10SK(Dip)LDS (PEG)2 10K, 13Dip, QAAQD(αMePhe)VE 17Q, 18A, (Aib)LANT-amide 22αMePhe, 24E, 25Aib, 27A Peptide HSQGS(αMePhe)TSDK 403 Stearoyl γE-γE- 10 Amide 5S, 397 ((PEG)2-(PEG)2-γE-γE- (PEG)2- 6αMePhe, Stearoyl)10SK(Dip)LDS (PEG)2 10K, 13Dip, (ß- 17ß- dimethylArg)AAQD dimethylR, (αMePhe)VEHLANT-amide 18A, 22αMePhe, 24E, 25H, 27A

TABLE 5 Peptides Modified at Position 13 Linker Sequence Albumin (described Acyl- modification SEQ ID binding N→C ation C- with respect Peptide Sequence NO moiety term.) site term. to glucagon Peptide HSQGS(αMePhe)TSDVS 404 Stearoyl γE-γE- 13 Amide 5S 398 KK((PEG)2-(PEG)2-γE- (PEG)2- 6αMePhe, γE-Stearoyl)13LDS(ß- (PEG)2 10V, 13K, dimethylArg)AAQD 17ß- (αMePhe)VE(Aib)LANT- dimethylR, amide 18A, 22αMePhe, 24E, 25Aib, 27A Peptide HSQGS(αMePhe)TSDVS 405 Palmitoyl γE-γE- 13 Amide 5S, 399 KK((PEG)2-(PEG)2-γE- (PEG)2- 6αMePhe, VE-Palmitoyl)13LDS(B- (PEG)2 10V, 13K, dimethylArg)AAQD(aM 17ß- ePhe)VE(Aib)LANT- dimethylR, amide 18A, 22αMePhe, 24E, 25Aib, 27A Peptide H(Aib)QGS(αMePhe)TS 406 Palmitoyl γE- 13 Amide 2Aib, 5S, 340 DVSKK((PEG)2-(PEG)2- (PEG)2- 6αMePhe, γE- (PEG)2 10V, 13K, Palmitoyl)13LDSRAAQ 18A, D(αMePhe)VEWIANT- 22αMePhe, amide 24E, 26I, 27A Peptide H(Aib)QGSFTSDVSKK 407 Palmitoyl γE- 13 Amide 2Aib, 5S, 341 ((PEG)2-(PEG)2-γE- (PEG)2- 10V, 13K, Palmitoyl)13LDSRAAQ (PEG)2 18A, 24E, DEVEWIANT-amide 26I, 27A Peptide HSQGS(αMePhe)TSDVS 408 Stearoyl γE-γE- 13 Amide 5S, 342 KK((PEG)2-(PEG)2-γE- (PEG)2- 6αMePhe, γE- (PEG)2 10V, 13K, Stearoyl)13LDSQAAQD 17Q, 18A, (αMePhe)VE(Aib)LANT- 22αMePhe, amide 24E, 25Aib, 27A Peptide HSQGS(αMePhe)TSDVS 409 Stearoyl γE-γE- 13 Amide 5S, 343 KK((PEG)2-(PEG)2-γE- (PEG)2- 6αMePhe, γE-Stearoyl)13LDS(ß- (PEG)2 10V, 13K, dimethylArg)AAQD 17ß- (αMePhe)VEHLANT-amide dimethylR, 18A, 22αMePhe, 24E, 25H, 27A Peptide H(Aib)HGS(αMePhe)TS 410 C20diacid γE-γE- 13 Amide 2Aib, 3H, 5S, 344 DVSKK(O2OC-O2OC-γE- (O2Oc)- 6αMePhe, γE- (O2Oc) 10V, 13K, C20diacid)13LDSRAAQ 18A, D(αMePhe)VQ(Aib)IAN 22αMePhe, T-amide 25Aib, 26I, 27A Peptide H(Aib)HGS(αMePhe)TS 411 C18diacid γE- 13 Amide 2Aib, 3H, 5S, 345 DVSKK(O2OC-O2OC-γE- (O2Oc)- 6αMePhe, C18diacid)13LDSRAAQ (O2Oc) 10V, 13K, D(αMePhe)VQ(Aib)IAN 18A, T-amide 22αMePhe, 25Aib, 26I, 27A

In some aspects, the peptide comprises the sequence: H-X2-X3-G-X5-X6-T-S-D-X10-S-X12-αMethyl-Phenylalanine (αMePhe)-L-X15-X16-X17-X18-A-X20-X21-X22-X23-X24-X25-X26-X27-X28-X29-X30-X31-Z, wherein X2 is Aminoisobutyric acid (Aib), S, or A, X3 is Q, H, or E, X5 is T or S, X6 is F or αMePhe, X10 is V, K or Y, X11 is S, X12 is K, E, or S, X15 is D or E, X16 is T, S, or G, X17 is K, R, E, or Q, X18 is R or A, X20 is R, K, or Q, X21 is D or E, X22 is αMePhe or F, X23 is V or I, X24 is Q or A, X25 is Aib or W, X26 is L or I, X27 is L, A, E, V, or M, X28 is E, N, A, R, or K, X29 is Aib, T, or G, X30 is G, R, or not present, X31 is G or not present, and Z is amide or acid (SEQ ID NO: 540).

In some aspects, X2 is Aib. In some aspects, X3 is Q. In some aspects, X3 is H. In some aspects, X5 is T. In some aspects, X5 is S. In some aspects, X6 is F. In some aspects, X6 is αMePhe. In some aspects, X10 is V. In some aspects, X12 is K. In some aspects, X15 is D. In some aspects, X16 is T. In some aspects, X16 is S. In some aspects, X17 is K. In some aspects, X17 is R. In some aspects, X18 is R. In some aspects, X18 is A. In some aspects, X20 is R. In some aspects, X20 is K. In some aspects, X21 is D. In some aspects, X22 is F. In some aspects, X22 is αMePhe. In some aspects, X23 is V. In some aspects, X24 is Q. In some aspects, X25 is W. In some aspects, X25 is Aib. In some aspects, X26 is L. In some aspects, X26 is I. In some aspects, X27 is L. In some aspects, X27 is A. In some aspects, X28 is E. In some aspects, X28 is N. In some aspects, X29 is Aib. In some aspects, X29 is T. In some aspects, X30 is G. In some aspects, X30 is not present. In some aspects, X31 is not present. In some aspects, Z is amide. In some aspects, Z is acid.

In some aspects, X2 is Aib, X12 is K, and X24 is Q. In some aspects, X16 is T, X17 is K, X27 is L, X28, is E, and X29 is Aib.

In some aspects, X3 is Q, X5 is T, X6 is F, X10 is V, X12 is K, X15 is D, X16 is T, X17 is K, X18 is R, X20 is R, X21 is D, X22 is F, X23 is V, X24 is Q, X25 is W, X26 is L, X27 is L, X28 is E, X29 is Aib, X30 is G, and X31 is not present.

In some aspects, X3 is H, X5 is S, X6 is αMePhe, X10 is V, X12 is K, X15 is D, X16 is S, X17 is R, X18 is A, X20 is K, X21 is D, X22 is αMePhe, X23 is V, X24 is Q, X25 is Aib, X26 is I, X27 is A, X28 is N, X29 is T, X30 is not present, and X31 is not present.

In some aspects, one or more lysine residues are acylated. In some aspects, the lysine at position 17 is acylated. In some aspects, the lysine at position 20 is acylated.

In some aspects, one or more lysine resides are lipidated. In some aspects, the lysine at position 17 is lipidated. In some aspects, the lysine at position 20 is lipidated.

In some aspects, the lipid is selected from the group consisting of octadecanedioic acid (C18diacid) and icosanedioic acid (C20diacid). In some aspects, the lipid is octadecanedioic acid (C18diacid). In some aspects, the lipid is icosanedioic acid (C20diacid).

In some aspects, the lipid is linked to the residue at position 17 or 20 via a linker. In some aspects, the linker is γE-(O2Oc)-(O2Oc) or γE-γE-(O2Oc)-(O2Oc). In some aspects, the linker is γE-(O2Oc)-(O2Oc). In some aspects, the linker is γE-γE-(O2Oc)-(O2Oc). In some aspects, the linker is linked to the epsilon amino group of the residue at position 17 or 20.

Certain aspects of the disclosure are directed to a peptide comprising the sequence of H-Aib-Q-G-T-F-T-S-D-V-S-K-αMePhe-L-D-T-K-R-A-R-D-F-V-Q-W-LL-E-Aib-G-acid (SEQ ID NO: 541).

In some aspects, the lysine at position 17 is acylated and lipidated, the lipid is linked to the acylated lysine via a (E-(O2Oc)-(O2Oc)-γE-C18diacid).

In some aspects, the lysine at position 17 is acylated and lipidated, the lipid is linked to the acylated lysine at position 17 via a (ε-(O2Oc)-(O2Oc)-γE-C20diacid).

Certain aspects of the disclosure are directed to a peptide comprising the sequence H-Aib-H-G-S-αMePhe-T-S-D-V-S-K-αMePhe-L-D-S-R-A-A-K(ε-(O2Oc)-(O2Oc)-γE-C18diacid)20-D-αMePhe-V-Q-Aib-I-A-N-T-amide (SEQ ID NO: 228).

Certain aspects of the disclosure are directed to a peptide comprising the sequence H-Aib-H-G-S-αMePhe-T-S-D-V-S-K-αMePhe-L-D-S-R-A-A-K(E-(O2Oc)-(O2Oc)-γE-γE-C20diacid)20-D-αMePhe-V-Q-Aib-I-A-N-T-amide (SEQ ID NO: 233).

In some aspects, the peptide binds to the GLP-1 receptor (GLP-1R), binds to the glucagon receptor (GCGR), or binds to both a GLP-1 receptor and a glucagon receptor. In some aspects, the GLP-1R is a human GLP-1R. In some aspects, the GCGR is a human GCGR. In some aspects, the peptide is an agonist of GLP-1 activity, an agonist of glucagon activity, or an agonist of both GLP-1 and glucagon activity.

In some aspects, the peptide has increased proteolytic-resistance relative to the natural ligand of the GLP-1R and/or GCGR.

In some aspects, the peptide is isolated.

In some aspects, the peptide has at least 50%, at least 60%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95, or 100% of intact peptide remaining after incubation with a protease at 37° C. for 5 min, 10 min, 15 min, 30 min, 2 hr, 4 hr or 24 hr. In some aspects, the protease is selected from the group consisting of neprilysin, pepsin, pancreatin, simulated gastric fluid with pepsin, and simulated intestinal fluid with pancreatin.

In some aspects, the peptide has a half-life in cynomolgus monkeys after intravenous administration of at least 45 hours, at least 50 hours, at least 60 hours, at least 70 hours, at least 80 hours, at least 90 hours, at least 100 hours, at least 110 hours, at least 120 hours, or about 130 hours.

In some aspects, the peptide has an s.c. bioavailability in cynomolgus monkeys of at least 75%, at least 80%, at least 90%, or about 95%.

III. Methods of Making GLP-1/Glucagon Agonist Peptides

GLP-1/glucagon agonist peptides for uses provided herein can be made by any suitable method. For example, in some aspects provided herein, the GLP-1/glucagon agonist peptides for uses provided herein are chemically synthesized by methods well known to those of ordinary skill in the art, e.g., by solid phase synthesis as described by Merrifield (1963, J. Am. Chem. Soc. 85:2149-2154). Solid phase peptide synthesis can be accomplished, e.g., by using automated synthesizers, using standard reagents, e.g., as explained in Example 1 of WO 2014/091316, which is herein incorporated by reference in its entirety.

Alternatively, GLP-1/glucagon agonist peptides for uses provided herein can be produced recombinantly using a convenient vector/host cell combination as would be well known to the person of ordinary skill in the art. A variety of methods are available for recombinantly producing GLP-1/glucagon agonist peptides. Generally, a polynucleotide sequence encoding the GLP-1/glucagon agonist peptide is inserted into an appropriate expression vehicle, e.g., a vector which contains the necessary elements for the transcription and translation of the inserted coding sequence. The nucleic acid encoding the GLP-1/glucagon agonist peptide is inserted into the vector in proper reading frame. The expression vector is then transfected into a suitable host cell which will express the GLP-1/glucagon agonist peptide. Suitable host cells include without limitation bacteria, yeast, or mammalian cells. A variety of commercially-available host-expression vector systems can be utilized to express the GLP-1/glucagon agonist peptides described herein.

Pharmaceutical Compositions

Further provided are compositions, e.g., pharmaceutical compositions, that contain an effective amount of a GLP-1/glucagon agonist peptide as provided herein, formulated for the treatment of metabolic diseases, e.g., obesity, type 2 diabetes, and/or NASH.

Compositions of the disclosure can be formulated according to known methods. Suitable preparation methods are described, for example, in Remington's Pharmaceutical Sciences, 19th Edition, A. R. Gennaro, ed., Mack Publishing Co., Easton, PA (1995), which is incorporated herein by reference in its entirety. Composition can be in a variety of forms, including, but not limited to an aqueous solution, an emulsion, a gel, a suspension, lyophilized form, or any other form known in the art. In addition, the composition can contain pharmaceutically acceptable additives including, for example, diluents, binders, stabilizers, and preservatives. Once formulated, compositions of the invention can be administered directly to the subject.

In some aspects, the pharmaceutical composition is a solid composition. In some aspects, the pharmaceutical composition is a liquid composition.

IV. Methods of Using GLP-1/Glucagon Agonist Peptides

As provided herein, GLP-1/glucagon agonist peptides can be used to improve glycemic control, reduce weight, type 2 diabetes mellitus (T2DM), and/or treat or prevent non-alcoholic steatohepatitis (NASH).

In some aspects, administration of the GLP-1/glucagon agonist peptides decreases body weight of the subject, increases insulin secretion in the subject, delays gastric emptying in the subject, decreases food intake in the subject, increases mitochondria function in the subject, inhibits de novo lipogenesis in the subject, decreases HbA1c in the subject, enhances fatty oxidation in the subject, decreases hepatic mitochondrial oxidative stress in the subject, decreases steatosis in the subject, decreases fibrosis in the subject, decreases glycogen synthesis in the subject, increases gluconeogenesis in the subject, halts disease progression in the subject, reverses fibrosis in the subject, and/or reduces risk of death due to cirrhosis, hepatocellular carcinoma, and/or cardiorenal disease in the subject.

As provided herein a method of improving glycemic control or reduce weight in a human subject with T2DM and/or NASH can comprise administering to the subject a GLP-1/glucagon agonist peptide.

This disclosure also provides a GLP-1/glucagon agonist peptide for use in the manufacture of a medicament for improving glycemic control or reduce weight in a human subject with T2DM and/or NASH.

In some aspects, the peptide is administered about once a week.

In some aspects, the GLP-1/glucagon agonist peptide is administered to treat or prevent a disease or condition cause or characterized by excess body weight. In some aspects, the disease or condition is obesity. In some aspects, the disease or condition is type 2 diabetes.

In some aspects, the GLP-1/glucagon agonist peptide is administered to treat or non-alcoholic steatohepatitis (NASH). In some aspects, the GLP-1/glucagon agonist peptide is administered by injection. In some aspects, the GLP-1/glucagon agonist peptide is administered orally. In some aspects, administration of the GLP-1/glucagon agonist peptide decreases body weight of the subject, increases insulin secretion in the subject, delays gastric emptying in the subject, decreases food intake in the subject, increases mitochondria function in the subject, inhibits de novo lipogenesis in the subject, decreases HbA1c in the subject, enhances fatty oxidation in the subject, decreases hepatic mitochondrial oxidative stress in the subject, decreases steatosis in the subject, decreases fibrosis in the subject, decreases glycogen synthesis in the subject, increases gluconeogenesis in the subject, halts disease progression in the subject, reverses fibrosis in the subject, and/or reduces risk of death due to cirrhosis, hepatocellular carcinoma, and/or cardiorenal disease in the subject. In some aspects, the subject is a human. In some aspects, the peptide is administered about once a week.

EXAMPLES Example 1: Lipidated-GLP-1/Glucagon Dual Agonist Peptide Analogue Preparation

Lipidated-GLP-1R/GCGR dual agonist peptides were synthesized as C-terminal carboxamides or carboxylic acids using rink amide MBHA resin (100-200 mesh) or Wang resin (100-200 mesh). All peptides were prepared by automated synthesis using a PTI Prelude solid phase peptide synthesizer using the 9-fluorenylmethoxycarbonyl (Fmoc)/tert-butyl (^(t)Bu) protocol. Manufacturer-supplied protocols were applied for coupling of amino acids in N,N-dimethylformamide (DMF) and deprotection of Fmoc protecting group using piperidine in DMF (20% v/v). Asparagine (Asn), glutamine (Gln) and histidine (His) were incorporated as their sidechain triphenylmethyl, trityl (Trt) derivatives. Lysine (Lys) was incorporated as the sidechain tert-butyloxycarbonyl (Boc) derivative. Serine (Ser), threonine (Thr) and tyrosine (Tyr) were incorporated as sidechain tBu ethers, and aspartate (Asp) and glutamate (Glu) as their sidechain O^(t)Bu esters. Arginine (Arg) was incorporated as the sidechain 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl (Pbf) derivative. Other amino acids were incorporated with an appropriate sidechain protection.

Lys(Mmt) was incorporated when a subsequent chemical modification of the lysine side chain was required. Upon completion of the peptide chain elongation, Mmt side chain protection was removed by treatment of the resin with selective deprotection cocktail (1% trifluoroacetic acid (TFA), 5% TIPS in dichloromethane (DCM)) at 100 mL/mmol for 1 min, and repeated at least 10 times until Mmt group deprotection was completed. The reaction was quenched with 10% N,N-diisopropylethylamine (DIPEA)/NMP. Subsequent coupling of a albumin binding moiety, such as a lipid and linker, was performed manually using 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU) as a coupling reagent in the presence of DIPEA.

Peptides were cleaved from the solid support by treatment with a mixture of TFA. triisopropylsilane (TIS):water (92.5.5:2.5 v/v) for 4 h with agitation at room temperature. Thereafter, the cleavage mixtures were filtered, concentrated in vacuo, precipitated and washed with diethyl ether and solids were isolated by centrifugation. The crude peptides were dried under a flow of nitrogen and dissolved in 20% acetonitrile (MeCN)/water (v/v) and filtered. The crude peptides were purified using a preparative reversed-phase high-performance liquid chromatography (RP-HPLC) on a Varian SD-1 Prep Star binary pump system, monitoring by ultraviolet (UV) absorption at 210 nm using an Xbridge C18-A stationary phase (19.0×250 mm, 5 micron) column eluting a linear solvent gradient of 25-70% MeCN (0.1% TFA v/v) in water (0.1% TFA v/v) over 25 min. The purified fractions were pooled, frozen and lyophilised.

Liquid chromatography/mass spectrometry (LC/MS) characterization of purified peptides were performed on a Waters MassLynx 3100 platform using a XBridge C18 stationary phase (4.6×100 mm, 3 micron) eluting a linear binary gradient of 10-90% MeCN (0.1% TFA v/v) in water (0.1% TFA v/v) over 10 minutes at 1.5 mL/min at ambient temperature. Analytes were detected by both UV absorption at 210 nm and ionization using a Waters 3100 mass detector (electrospray ionisation (ESI)+ mode). Analytical RP-HPLC characterization was performed on an Agilent 1260 Infinity system using an Agilent Polaris CS-A stationary phase (4.6×100 mm, 3 micron) eluting a linear binary gradient of 10-90% MeCN (0.1% TFA v/v) in water (0.1% TFA v/v) at 1.5 mL/min over 15 minutes at 40° C.

Example 2: GLP-1 Receptor and Glucagon Receptor In Vitro Functional Assay

The functional activities of lipidated-GLP-1R/GCGR peptides, such as cAMP production, were tested in CHO cell line with stable recombinant expression of human GLP-1 receptor (hGLP-1R) or human glucagon receptor (hGCGR).

Cryopreserved cell stocks were thawed rapidly in a water-bath, suspended in assay buffer (0.1% BSA (Sigma #A3059) in HBSS (Sigma #H8264) with 25 mM HEPES, pH 7.4 and containing 0.5 mM IBMX (Sigma #17018)) and centrifuged at 240×g for 5 minutes. Cells were re-suspended in assay buffer at a batch-dependent optimized concentration (typically hGLP-1R cells at 1×10⁵ cells/mL, hGCGR cells at 2×10⁵ cells/mL).

The test peptide stock was prepared in DMSO and serially diluted in assay buffer to prepare 11-point concentration response curves, in duplicate, in 384-well low volume microtiter assay plates (Corning #4514) using a non-contact liquid dispenser (ECHO™, LabCyte). Cells were added to the assay plate using a multidrop dispenser and incubated at room temperature for 30 minutes before measuring the cAMP level using a cAMP dynamic 2 homogeneous time resolved Fluorescence (HTRF) kit (Cisbio Bioassays #62AM4PEJ) following the two-step protocol as per manufacturer's recommendations. In brief, anti-cAMP cryptate (donor fluorophore) and cAMP-d2 (acceptor fluorophore) were made up separately by diluting each 1 in 20 in conjugate and lysis buffer provided in the kit. Anti-cAMP cryptate was added to all wells of the assay plate, followed by cAMP-d2 added to all wells except non-specific binding (NSB) wells (to which conjugate and lysis buffer was added). Plates were incubated at room temperature for one hour and then read on an Envision (Perkin Elmer) using an excitation wavelength of 320 nm and emission wavelengths of 620 nm & 665 nm.

Data was transformed to % Delta F as described in the manufacturer's guidelines and analyzed by 4-parameter logistic fit to determine EC₅₀ values. The selectivity ratio of a peptide to hGLP-1R vs hGCGR is defined as: % Relative Potency Ratio=% GLP-1R activity relative to GLP-1/% GlucR activity relative to glucagon. Data is shown as the geometric mean EC₅₀ (pM) from >n=2 independent experiments.

The relative potency ratios of peptides is listed in Tables 6-10.

TABLE 6 Potency of Peptides with Modification on Amino Acid at Position 17 hGLP-1R hGluc-R % Relative Peptide EC₅₀ (pM) EC₅₀ (pM) Potency Ratio GLP-1(7-36) amide 2.196 — — Glucagon — 1.110 — 1 3197.264 >27100 — 2 1281.484 4192.851 6.5 3 69.013 149.198 4.3 4 240.004 1167.129 9.6 5 282.756 7137.899 49.9 6 567.937 516.038 1.8 7 84.551 30.666 0.7 8 87.845 53.635 1.2 9 241.876 278.726 2.3 10 657.981 376.720 1.1 11 156.625 117.572 1.5 12 14.531 47.666 6.5 13 15.895 44.043 5.5 14 93.788 462.195 9.7 15 33.122 61.419 3.7 16 32.959 104.788 6.3 17 44.976 134.979 5.9 18 20.493 121.569 11.7 19 38.345 133.477 6.9 20 152.448 135.633 1.8 21 377.683 68.754 0.4 22 1226.703 2724.463 4.4 23 266.349 321.178 2.4 24 82.803 101.130 2.4 25 725.678 1311.347 3.6 26 80.600 8904.381 218.5 27 18.189 1438.437 156.4 28 129.321 259.647 4.0 29 106.638 629.359 11.7 30 52.683 234.982 8.8 31 41.292 56.793 2.7 40 29.909 123.325 8.2 41 662.690 5737.086 17.1 42 665.048 8189.848 24.4 136 45.196 509.273 22.3 137 143.435 267.783 3.7 138 104.274 183.767 3.5 139 630.031 983.762 3.1 140 22.725 46.408 4.0 141 263.906 392.259 2.9 142 59.361 107.506 3.6 143 19.134 32.638 3.4 144 45.230 702.417 30.7 145 22.618 4587.203 401.2 146 24.628 1634.605 131.3 147 15.328 43.496 5.6 148 40.233 567.838 27.9 149 8.707 2653.203 602.8 150 166.473 355.432 4.2 151 111.202 178.430 3.2 152 11.912 20.350 3.4 153 41.161 99.002 4.8 158 303.611 332.670 2.2 159 145.208 144.564 2.0 160 55.178 416.851 14.9 162 59.567 1027.507 34.1 161 50.942 1030.580 40.0 166 48.005 269.638 11.1 167 76.814 310.656 8.0 43 1.894 5.520 5.8 44 2.117 18.235 17.0 45 2.028 14.943 14.6 46 3.395 5.914 3.4 47 1.715 2.381 2.7 48 19.862 43.244 4.3 49 1.738 1.728 2.0 50 4.903 8.738 3.5 51 18.101 41.930 4.6 52 22.733 6.646 0.6 53 3.025 18.850 12.3 54 2.810 2.588 1.8 55 18.800 19.085 2.0 56 4.860 10.909 4.4 57 9.093 16.912 3.7 58 3.900 11.329 5.7 59 6.181 28.350 9.1 60 5.161 21.118 8.1 61 4.125 9.554 4.6 62 10.098 15.204 3.0 63 3.139 2.488 1.6 64 2.574 3.065 2.4 65 1230.000 2060.580 3.3 66 1.524 6.426 8.3 67 2.432 9.488 7.7 68 1.095 4.670 8.4 69 1.145 6.442 11.1 70 1.550 30.865 39.4 71 2.174 53.722 48.9 72 3.418 73.660 42.6 73 0.275 21.956 157.9 74 1.831 10.893 11.8 75 18.897 2803.488 293.5 76 1.776 339.882 378.6 77 8.682 243.406 55.5 78 1.135 8.972 15.6 79 1.733 10.679 12.2 80 1.033 9.179 17.6 81 1.188 13.543 22.6 82 0.839 7.774 18.3 83 1.043 15.604 29.6 84 2.798 44.887 31.7 85 1.038 47.687 90.9 86 0.772 6.459 16.6 87 1.289 8.465 13.0 88 1.040 6.467 12.3 89 3.769 15.282 8.0 90 1.866 6.606 7.0 91 1.570 7.797 9.8 92 0.895 10.899 24.1 93 0.472 8.920 37.4 94 0.515 5.397 20.7 95 0.608 12.464 40.6 96 0.851 30.053 69.9 97 1.055 12.962 24.3 98 2.442 54.125 43.8 99 2.212 33.196 29.7 100 0.258 40.473 310.3 101 0.713 119.000 330.1 102 0.231 26.508 227.0 103 0.532 59.381 220.8 104 246.670 45.636 0.4 105 64.817 121.121 3.7 106 6.819 36.794 10.7 107 65.867 99.074 3.0 108 3197.264 >27100.000 — 109 697.596 >26800.000 — 110 0.627 48.465 152.9 111 1.918 2.090 2.2 112 3.364 2.689 1.6 113 1.613 4.603 5.6 114 3.647 2.648 1.4 117 15.615 2.990 0.4 116 24.329 10.308 0.8 117 1.398 1.848 2.6 118 1.068 1.201 2.2 119 1.392 1.700 2.4 120 1.810 2.616 2.9 121 1.502 1.200 1.6 122 1.417 0.857 1.2 123 0.496 12.883 51.4 124 1.274 9.790 15.2 125 0.575 6.676 23.0 128 0.594 10.997 36.6 127 0.998 12.649 25.1 128 0.788 4.695 11.8 129 0.462 4.100 17.6 130 1.087 32.889 59.9 131 0.511 17.811 68.9 132 0.949 34.315 71.5 133 1.060 29.964 55.9 134 0.592 15.008 50.1 135 0.407 14.984 72.8 407 208.719 462.060 4.4 408 370.323 828.459 4.4 409 22.673 203.000 17.7 410 78.013 455.043 11.5 411 98.122 377.956 7.6 412 185.707 397.402 4.2 413 406.086 1023.554 5.0 414 32.273 26.904 1.6 415 14.693 301.237 40.6 416 67.741 581.428 17.0 417 33.876 16.440 1.0 418 88.091 221.794 5.0 419 96.888 264.191 5.4 420 23.104 36.906 3.2 421 87.299 179.876 4.1 422 27.559 123.460 8.9 423 26.123 2219.743 168.1 424 15.540 129.497 16.5 425 11.490 826.662 142.3 426 7.303 61.169 16.6 427 12.433 47.225 7.5 428 33.081 10.501 0.6 429 15.013 144.446 19.0 430 24.421 160.262 13.0 431 44.587 193.903 8.6 432 1377.330 1164.734 1.7 433 4464.399 10463.230 4.6 434 152.763 293.928 3.8 435 22.659 240.076 21.0 436 7.427 68.750 18.3 437 26.892 96.876 7.1 438 17.923 68.908 7.6 439 30.650 57.730 3.7 440 153.518 81.008 1.0 441 62.730 72.810 2.3 442 19.052 35.819 3.7 443 20.559 22.434 2.2 444 247.415 1758.388 14.1 445 33.016 683.673 41.0 446 32.889 365.880 22.0 447 169.598 666.503 7.8 448 53.134 28.953 1.1 449 207.17 241.70 2.3 450 57.318 57.789 2.0 451 894.881 503.273 1.1 452 495.050 150.934 0.6 453 169.523 161.692 1.9 454 173.343 273.630 3.1 455 127.140 114.432 1.8 456 132.866 80.328 1.2 457 109.278 202.834 3.7 458 114.344 384.540 6.7 459 32.674 36.947 2.2 460 116.724 66.478 1.1 461 167.051 Not tested — 462 39.497 89.240 4.5 463 273.563 Not tested — 464 Not tested Not tested — 465 485.020 436.382 1.8 466 35.571 131.195 7.3 467 Not tested Not tested — 468 67.532 292.374 8.6 469 254.776 538.155 4.2 470 55.908 30.269 1.1 471 101.756 63.584 1.2 472 7.627 11.060 2.9 473 11.463 14.135 2.4 474 8.043 56.901 14.0 475 6.748 61.516 18.0 476 57.309 103.924 3.6 477 54.091 117.426 4.3 478 9.178 189.932 40.9 479 34.154 206.779 12.0 480 12.573 136.201 21.4 481 52.209 349.837 13.3 482 190.311 691.097 7.2 483 177.661 168.551 1.9 484 338.595 168.884 1.0 485 219.193 90.425 0.8 486 420.381 166.466 0.8 487 65.455 164.468 5.0 488 201.998 300.737 2.9 489 22.787 167.608 14.5 490 69.046 396.488 11.4 491 73.584 231.822 6.2 492 212.412 374.486 3.5 493 23.450 165.822 14.0 494 98.727 212.207 4.3 495 23.165 379.702 32.4 496 64.887 482.010 14.7 497 37.397 118.244 6.3 498 156.406 169.974 2.1 499 40.647 78.787 3.8 500 101.880 101.482 2.0 501 26.516 75.630 5.6 502 82.090 174.964 4.2 503 81.209 84.902 2.1 504 123.927 551.274 8.8 505 42.121 190.780 9.0 506 162.104 148.973 1.8 507 52.850 86.602 3.2 508 67.930 2802.216 81.6 509 594.123 3020.408 10.1 510 176.244 117.832 1.3 511 117.715 139.920 2.4 512 159.226 2308.999 28.7 513 93.821 1340.613 28.3 514 76.660 1373.731 35.4 515 296.991 2659.628 17.7 516 137.100 784.568 11.3 517 145.751 737.919 10.0 136 45.196 509.273 22.3 137 143.435 267.783 3.7 138 104.274 183.767 3.5 139 630.031 983.762 3.1 140 22.725 46.408 4.0 141 263.906 392.259 2.9 142 59.361 107.506 3.6 143 19.134 32.638 3.4 144 45.230 702.417 30.7 145 22.618 4587.203 401.2 146 24.628 1634.605 131.3 147 15.328 43.496 5.6 148 40.233 567.838 27.9 149 8.707 2653.203 602.8 150 166.473 355.432 4.2 151 111.202 178.430 3.2 152 11.912 20.350 3.4 153 41.161 99.002 4.8 158 303.611 332.670 2.2 159 145.208 144.564 2.0 160 55.178 416.851 14.9 162 59.567 1027.507 34.1 165 50.942 1030.580 40.0 166 48.005 269.638 11.1 167 76.814 310.656 8.0 518 31.000 77.320 4.9 519 172.230 385.880 4.4 520 542.600 1616.230 5.9 32 12.953 240.474 36.7 33 213.123 548.248 5.1 34 82.377 160.622 3.9 35 83.697 334.904 7.9 36 43.060 277.733 12.8 37 68.620 2748.412 79.2 38 75.589 441.481 11.6 39 76.068 193.860 5.0 161 17.234 188.040 21.6 163 90.154 143.715 3.2 168 447.505 886.110 3.9 169 210.397 1404.311 13.2 170 147.744 835.556 11.2 171 106.863 376.304 7.0 172 213.354 1273.732 11.8 173 134.317 874.131 12.9 174 127.027 420.420 6.5 175 68.376 2018.944 58.4 176 59.942 480.338 15.9 177 23.777 306.464 25.5 178 51.770 104.397 4.0 179 130.928 203.431 3.1 180 24.377 71.735 5.8 181 56.000 33.440 1.2 182 29.060 22.580 1.5 183 23.730 81.430 6.8 184 22.040 29.620 2.7 185 44.113 229.651 10.3 186 44.923 100.835 4.4 188 20.847 34.713 3.3 189 11.315 44.301 7.7 192 107.568 227.117 4.2 193 282.849 476.105 3.3 194 424.799 592.863 2.8 195 86.016 94.577 2.2 196 26.953 240.329 17.6 197 64.040 111.890 3.5 198 211.810 302.200 2.8 199 31.604 180.232 11.3 200 22.687 97.711 8.5 201 22.724 182.560 15.9 202 17.824 242.436 26.9

TABLE 7 Potency of Peptides with Modification on Amino Acid at Position 20 hGLP-1R hGluc-R % Relative Peptide EC₅₀ (pM) EC₅₀ (pM) Potency Ratio 203 77.466 34.112 0.9 204 43.306 595.006 27.2 205 29.901 8.136 0.5 206 70.949 18.170 0.5 207 177.618 96.175 1.1 208 64.412 658.298 20.2 209 126.544 42.591 0.7 210 156.403 93.732 1.2 211 166.600 60.904 0.7 212 531.595 97.476 0.4 213 534.307 140.535 0.5 214 2339.231 809.862 0.7 215 7623.287 2609.521 0.7 216 18055.470 5672.548 0.6 217 263.939 126.681 0.9 218 138.770 422.882 6.0 219 94.472 297.862 6.2 220 240.450 405.230 3.3 221 122.449 122.801 2.0 222 151.493 243.967 3.2 223 48.761 103.522 4.2 224 32.095 28.693 1.8 225 34.873 144.655 8.2 226 82.675 27.435 0.7 227 70.467 27.208 0.8 228 200.219 176.842 1.7 229 68.511 198.144 5.7 230 170.050 37.108 0.4 231 49.851 58.542 2.3 232 110.306 1023.865 18.4 233 440.364 407.411 1.8 234 68.020 1285.410 37.4 235 94.790 1262.350 26.3 236 22.063 214.558 19.2 237 26.745 298.747 22.1 238 154.658 990.172 12.7 239 105.489 704.613 13.2 240 57.099 332.464 11.5 241 35.843 175.226 9.7 242 248.687 1234.326 9.8 243 59.292 50.633 1.7 244 143.475 420.232 5.8 245 110.173 62.682 1.1 246 320.437 556.602 3.4 247 84.851 51.143 1.2 248 1089.266 13553.228 24.6 249 558.256 545.142 1.9 250 601.166 1566.333 5.2 251 79.751 248.071 6.2 252 119.246 1309.962 21.7 253 75.451 53.089 1.4 254 101.863 125.276 2.4 255 147.550 145.739 2.0 256 345.977 1306.254 7.5 257 7.348 1.659 0.4 258 34.046 93.123 5.4 259 19.118 34.833 3.6 260 33.080 76.881 4.6 261 16.152 29.390 3.6 262 13.017 11.700 1.8 263 25.386 64.646 5.0 264 69.537 297.466 8.5 265 71.223 130.903 3.6 266 66.478 293.480 8.7 267 65.581 127.683 3.9 268 39.521 29.251 1.5 269 51.951 271.143 10.3 270 24.445 31.318 2.5 271 54.604 27.999 1.0 272 15.650 14.309 1.8 273 22.118 23.336 2.1 274 27.112 31.277 2.3 275 110.638 175.236 3.1 276 143.383 91.395 1.3 277 49.494 57.270 2.3 278 78.855 83.493 2.1 279 86.544 150.224 3.4 280 78.346 154.623 3.9 281 155.104 1042.071 13.3 282 1230.958 1135.696 1.8 283 129.487 552.440 8.4 284 43.422 118.686 5.4 285 300.590 87.044 0.6 286 31.616 52.951 3.3 287 27.519 26.538 1.9 288 42.719 26.875 1.2 289 118.366 148.058 2.5 290 346.546 260.062 1.5 291 1509.011 847.167 1.1 292 28.705 20.397 1.4 293 91.968 33.473 0.7 294 510.108 102.417 0.4 295 312.053 17071.588 108.2 296 64.149 3253.412 100.3 297 30.440 103.940 6.8 298 75.450 572.856 15.0 299 75.820 193.220 5.0 300 19.742 18.360 1.8 301 55.339 31.826 1.1 302 151.070 270.815 3.5 303 99.136 99.581 2.0 304 238.821 687.098 5.7 305 211.193 154.945 1.5 306 47.214 775.451 32.5 307 22.180 1126.909 100.5 308 27.499 1716.004 123.4 309 70.607 17377.186 486.8 310 56.382 1836.826 64.4 311 35.100 468.731 26.4 312 152.183 2775.255 36.1 313 138.271 1227.004 17.6 314 30.764 6832.600 439.3 315 18.118 5853.796 639.1 318 55.250 12001.370 429.7 321 22.635 4402.316 384.7 322 68.302 >24663.650 — 323 11406.357 >25553.360 — 324 1329.728 1927.309 2.9 325 928.583 >25546.770 — 326 6741.438 >25645.230 — 327 30.097 >25671.500 — 328 15.357 1698.302 218.8 330 487.667 >25645.230 — 331 62.577 66.606 2.1 332 77.474 58.853 1.5 333 134.727 212.627 3.1 334 249.757 461.777 3.7 335 1060.440 311.556 0.6 336 631.959 304.533 1.0 337 400.475 89.638 0.4 338 307.997 25.677 0.2 339 311.774 70.289 0.4 340 312.126 94.738 0.6 341 362.926 72.771 0.4 342 220.158 4832.731 43.4 343 198.013 19629.289 196.1 521 677.458 10099.850 29.5 522 508.426 6363.603 24.8 523 615.272 >24743.230 — 524 365.830 >24393.160 — 525 177.315 2454.700 27.4 526 194.459 689.991 7.0

TABLE 8 Potency of Peptides with Modification on Amino Acid at Position 24 hGLP-1R hGluc-R % Relative Peptide EC₅₀ (pM) EC₅₀ (pM) Potency Ratio 343 58.553 125.666 4.2 344 134.933 >26900.000 — 345 2860.629 167.753 0.1 346 7318.019 202.791 0.1 347 4971.036 596.962 0.2 348 70.074 4107.919 116.0 349 121.061 83.684 1.4 350 88.617 383.622 8.6 351 605.282 216.444 0.7 352 192.562 139.241 1.4 353 311.480 162.628 1.0 354 1106.278 901.878 1.6 355 424.009 478.456 2.2 356 304.243 315.728 2.1 357 916.728 550.189 1.2 358 74.855 16049.922 424.1 359 46.101 5048.643 216.6 360 107.773 5640.213 103.5 361 35.698 23.565 1.3 362 54.824 42.799 1.5 363 18.268 47.517 5.1 364 23.354 30.435 2.6 365 51.340 8.774 0.3 366 31.038 27.411 1.7 367 139.499 72.449 1.0 368 186.325 290.003 3.1 369 103.653 201.633 3.8 370 323.469 182.253 1.1 371 190.869 87.178 0.9 372 71.789 35.094 1.0 373 66.677 242.458 7.2 374 434.390 260.160 1.2 375 225.465 154.858 1.4 376 155.910 853.499 10.8 377 149.787 189.515 2.5 378 158.745 157.793 2.0 379 71.766 85.739 2.4 380 871.183 14947.910 33.9 381 174.069 1308.052 14.9 382 56.012 329.333 11.6 383 197.271 231.689 2.3 384 796.819 1244.347 3.1 386 31.186 140.185 8.9 387 82.603 1573.075 37.7 388 52.732 71.929 2.7 389 224.224 135.698 1.2

TABLE 9 Potency of Peptides with Modification on Amino Acid at Position 10 hGLP-1R hGluc-R % Relative Peptide EC₅₀ (pM) EC₅₀ (pM) Potency Ratio 391 892.536 22172.801 49.1 392 312.355 6922.306 43.8 393 0.458 2.158 9.3 394 0.652 2.408 7.3 395 0.774 9.554 24.4 396 0.583 11.835 40.2 397 5.360 10.003 3.7 398 3.280 2.449 1.5

TABLE 10 Potency of Peptides with Modification on Amino Acid at Position 13 hGLP-1R hGluc-R % Relative Peptide EC₅₀ (pM) EC₅₀ (pM) Potency Ratio 399 0.672 5.567 16.4 400 1.268 10.714 16.7 401 0.585 9.542 32.3 402 1.044 18.081 34.3 404 5.652 21.821 7.6 405 1041.139 8585.500 16.3 406 457.645 7308.311 31.6

Example 3: Mouse Acute Food Intake Study

Male C57Bl/6 mice obtained from Jackson Laboratories or Charles River at 8-9 weeks of age and were housed one per cage in BioDaq (Research Diets) cages. Mice were placed on Alpha Dri bedding, standard chow diet (Envigo, 2018) and given water pouches. Mice were allowed to acclimate for 1-2 weeks. Body weight was measured to ensure appropriate acclimation. After acclimation, mice were sham dosed a minimum of 2 times prior to initiation of food intake study. On study day, mice were placed in clean cage bottoms, weighed, and fasted for 6-8 hours. Mice were sorted into groups based on average 24-hour food intake data and body weight. 1-2 hours prior to lights out, mice were dosed subcutaneously with one vehicle or test peptide dissolved in an appropriate vehicle at 5 mL/kg. Mice were left undisturbed and allowed access to food and water for 48 hours. Automated food intake was monitored in the BioDaq system was monitored during this time. Discrete food intake data was exported into MS Excel from which cumulative food intake data was generated and analyzed. Food intake at 24 hours compared to vehicle food intake (percent) is provided in Table 11.

TABLE 11 Food Intake of Mice Administered Lipidated Peptides 24 hr % Vehicle Standard Error Peptide Dose Food Intake of the Mean (SEM) 43 10 nmol/kg 53.2 4.9 46 10 nmol/kg 72.1 4.3 47 10 nmol/kg 51.4 4.9 49 10 nmol/kg 69.2 9.0 50 10 nmol/kg 78.5 4.1 69 10 nmol/kg 74.3 4.6 68 10 nmol/kg 74.2 4.2 96 10 nmol/kg 51.9 5.5 62 10 nmol/kg 52.7 3.1 63 10 nmol/kg 37.9 7.0 71 10 nmol/kg 80.6 11.5 45 10 nmol/kg 76.2 4.7 399 10 nmol/kg 72.3 9.6 102 10 nmol/kg 81.9 14.6 73 10 nmol/kg 63.4 4.2 7 10 nmol/kg 55.0 4.0 349 10 nmol/kg 79.9 4.2 203 10 nmol/kg 81.4 7.3 361 10 nmol/kg 78.8 5.3 364 10 nmol/kg 63.7 5.5 366 10 nmol/kg 83.5 9.4 223 10 nmol/kg 63.6 6.3 229 10 nmol/kg 54.8 5.6 224 10 nmol/kg 66.5 7.8 375 10 nmol/kg 66.0 7.7 247 10 nmol/kg 66.9 5.5 257 3 nmol/kg 94.7 6.6 257 10 nmol/kg 96.5 3.7 224 1 nmol/kg 91.3 10.9 224 3 nmol/kg 76.6 3.3 224 10 nmol/kg 72.5 8.3 229 1 nmol/kg 86.0 4.7 229 3 nmol/kg 72.5 3.6 229 10 nmol/kg 50.5 3.7 289 3 nmol/kg 76.1 6.9 289 10 nmol/kg 49.6 6.7 299 30 nmol/kg 43.7 7.3 301 10 nmol/kg 54.9 7.6 300 10 nmol/kg 45.2 6.5 302 30 nmol/kg 46.4 9.5 140 10 nmol/kg 65.4 5.5 195 10 nmol/kg 58.2 8.7 188 10 nmol/kg 60.7 6.3 188 1 nmol/kg 99.9 6.3 188 3 nmol/kg 80.6 5.6 188 10 nmol/kg 49.8 5.1 195 1 nmol/kg 102.1 16.9 195 3 nmol/kg 84.0 13.3 195 10 nmol/kg 49.9 4.4

Example 4: Evaluating Proteolytic-Resistance of Lipidated Peptides to Fasted State Stimulated Gastric Fluid (FasSSGF) Containing Porcine Pancreatic Pepsin

Lyophilized porcine pancreatic pepsin (Sigma: P7012) was reconstituted to 0.5 mg/mL (˜2500 units/mL) in freshly prepared FasSSGF (Biorelevant media) to give the enzyme stock solution. Peptide stock solution was prepared to a concentration of 250 μM (˜1.0 mg/mL) in FasSSGF. 200 μL (10 μg, ˜250 units) of pepsin stock solution was added to 200 μL of peptide solution (1.0 mg/mL, ˜100 μg of peptide, ˜25 nmoles) and the mixture was co-incubated in a temperature-regulated incubator at 37° C. for the duration of the experiment. 30 μL aliquot of the peptide-enzyme mixture was periodically withdrawn (t=0, 5, 10, 15, and 30 min) and quenched immediately by addition of 80 μL of 0.1 M ammonium bicarbonate solution in water/acetonitrile (4:1, pH 8) to arrest proteolytic activity. 30 μL aliquot was analyzed by analytical RP-HPLC. Analytical RP-HPLC method: Agilent Polaris C8-A column (4.6×100 mm, 3 micron) eluted with a linear binary gradient of 10-90°/MeCN (0.1% TFA v/v) in water (0.1% TFA v/v) over either 10 or 15 mins at 1.5 mL min-1 at 40° C. with detection by UV absorption at 210 nm. Manual integration (AUC) allowed estimation of remaining intact peptide over the time course of the experiment. Peptide stability data is provided in Table 12.

TABLE 12 Stability of Lipidated Peptides Incubated with FasSSGF % intact peptide over time (min) Peptide 0 5 10 15 30 Semaglutide 100 15 13 12 14 7 100 81 60 35 18 229 100 100 97 91 79 15 100 ND ND 91 77 78 100 ND ND 100 100 290 100 ND ND 0 0 282 100 ND ND 83 76 283 100 ND ND 68 48 287 100 ND ND 0 0 367 100 ND ND 0 0

Example 5: Evaluating Proteolytic Resistance of Peptides to Neprilysin

10.0 μg (˜10 units) recombinant Neprilysin (R&D Systems: 1182-ZNC-010) was reconstituted to 100 μL (100 μg/mL, ˜100 units/mL) in assay buffer (50 mM Tris, 50 mM NaCl, 50 mM NaHCO₃, adjusted to pH 8.3) to give the enzyme stock solution. Peptide stock solutions were prepared to a concentration of ˜250 μM (˜1.0 mg/mL of 4 kDa peptide) in assay buffer. 100 μL (10 μg, ˜10 units) of neprilysin stock solution was added to 100 μL of peptide stock solution (1.0 mg/mL, ˜100 μg of peptide) and the mixture was co-incubated in a temperature regulated incubator at 37° C. for the duration of the experiment. 25 μL aliquots (˜12.5 μg initial peptide) of the peptide-enzyme mixture were periodically withdrawn (t=0, 30 mins, 1 h, 2 h, 4 h and 24 h) and quenched immediately by addition to an equal volume (75 μL) of 10% TFA (v/v) in 1:1 water/acetonitrile to arrest proteolytic activity. The quenched aliquot centrifuged at 7800 rpm, and 30 μL of the supernatant was analyzed by analytical RP-HPLC as follows: Analytical RP-HPLC method: Agilent Polaris C8-A column (4.6×100 mm, 3 micron) eluted with a linear binary gradient of 10-90% MeCN (0.1% TFA v/v) in water (0.1% TFA v/v) over either 10 or 15 mins at 1.5 mL min⁻¹ at 40° C. with detection by UV absorption at 210 nm. Manual integration (AUC) allowed estimation of remaining intact peptide over the time course of the experiment. Peptide stability data is provided in Table 13.

TABLE 13 Stability of Lipidated Peptides Incubated with Neprilysin % intact peptide over time Peptide 0 30 min 2 hr 4 hr 24 hr Semaglutide 100 100 100 83 48 7 100 100 100 97 84 229 100 100 100 100 100 15 100 ND ND 100 83 78 100 ND ND 100 100 290 100 ND ND 89 82 282 100 ND ND 100 97 283 100 ND ND 81 63 287 100 ND ND 77 59

Example 6: Evaluating Proteolytic-Resistance of Mono-Lipidated Peptides to Fasted-State Simulated Intestinal Fluid (FasSSIF/Pancreatin)

A fresh suspension of FasSSIF/P (Fasted-State Simulated Intestinal Fluid+USP Pancreatin®) was prepared according to that described by Galia, Nicolaides, Horter, Löbenberg, Reppas and Dressman: Pharm. Res. 15 (1998) 698-70.5, and USP XL requirements. The preparation of FasSSIF/P is provided in Table 14. The resulting preparation was used immediately without storage.

TABLE 14 Preparation of FasSSIF/Pancreatin Conc. Mol. Mass Supplier Composition mM Weight L−1 data Sodium Taurocholate 3 537.68 1.61 g Sigma: 86339 hydrate L-α-phosphatidylcholine 0.5 av. 768 0.38 g Sigma: 44924 (soybean) Dibasic sodium phosphate 30 141.96 4.26 g Sigma: S7907 Sodium hydroxide 10 40.00 0.40 g Sigma: S8045 Sodium Chloride 100 58.44 5.84 g Sigma: S7653 Pancreatin (8 × USP) — 1.25 g Sigma: P7545

Peptide for evaluation (1.0 mg) was dissolved in pre-warmed FasSSIF without Pancreatin® (200 μL). To this fresh FasSSIF/Pancreatin® (100 μL) was added to initiate potential proteolysis. Following momentary vortexing of the reaction tube the mixture was incubated at 37° C. in a thermostatic water bath for the duration of the experiment. 25 μL aliquot of the co-incubated peptide-enzyme mixture was periodically withdrawn (t=0, 5, 10 15 and 30 min) and quenched immediately by addition to a solution of 10% TFA in 1:1 water/acetonitrile (75 μL) to arrest proteolytic activity. Quenched samples were centrifuged (7800 RPM, 3 mins) to pellet solids and 10 μL aliquots of the supernatant solution were analyzed using analytical RP-HPLC as follows: Analytical RP-HPLC method: Agilent Polaris C8-A column (4.6×100 mm, 3 micron) eluted with a linear binary gradient of 10-90% MeCN (0.1% TFA v/v) in water (0.1% TFA v/v) over either 10 or 15 mins at 1.5 mL min⁻¹ at 40° C. with detection by UV absorption at 210 nm. Manual integration (AUC) allowed estimation of remaining intact peptide over the time course of the experiment. Peptide stability data is provided in Table 15.

TABLE 15 Stability of Lipidated Peptides Incubated with FasSSIF. % intact peptide over time (min) Peptide 0 5 10 15 30 Semaglutide 100 22 0 0 0 7 100 96 98 96 94 229 100 60 46 33 26 78 100 83 76 69 58 47 100 90 88 83 75 49 100 97 96 95 90 117 100 54 35 22 8 43 100 83 33 29 19 48 100 ND ND ND 94 50 100 ND ND ND 98 51 100 ND ND ND 91 52 100 ND ND ND 90 53 100 ND ND ND 92

Example 7: Glucose Levels in GLP-1R Knockout Mice Treated with GLP-1/Glucagon Peptides

GLP-JR knockout (KG) and wildtype (WT) mice at 8-14 weeks of age were singly housed on standard chow diet (Envigo, 2918) and automatic water. They acclimated for a minimum of ˜1-2 weeks, and mice were sorted into groups (n=4-8/group) based on body weight. On day of study, mice were fasted briefly for 2 hrs prior to study start. In some studies, mice were pre-treated with octreotide (BaChem, 10 mg/kg) at 30 minutes prior to peptide injection. Mice were dosed by subcutaneous injection, with peptide administration at doses listed in the Tables 16 and 17. Glucose was measured via glucometer at various timepoints including −30 min (prior to octreotide when used in studies), 0 min (before peptide dose), 30, 60, 120, 180, 240, and 360 minutes. Since these studies are acute in nature, mice were re-used for multiple studies (no more than 3) and always allowed at least a minimum wash-out period of 1 week. Glucose changes represented as percent glucose change (at 60 or 120 min) from time 0 min are provided in Tables 16 and 17.

TABLE 16 Glucose Change in GLP-1R KO and WT Mice Treated with GLP-1/Glucagon Peptides GLP-1R WT % KO % KO % glucose glucose glucose change WT change change Somatostatin Peptide Dose 120 min SEM 120 min SEM pretreatment? Vehicle 5 mL/kg 0.9 6.3 −0.7 7.6 No 78 3 nmol/kg −42.0 2.1 51.3 15.4 No Vehicle 5 mL/kg −19.2 6.7 −9.1 9.5 No 69 3 nmol/kg −27.2 7.7 17.6 4.8 No 43 3 nmol/kg −56.0 4.7 63.9 39.2 No Vehicle 5 mL/kg 43.3 12.6 72.4 24.9 yes 30 min prior to cpd 49 10 nmol/kg −1.2 7.2 193.3 16.2 yes 30 min prior to cpd 49 30 nmol/kg 16.8 25.9 154.3 17.0 yes 30 min prior to cpd Vehicle 5 mL/kg 28.6 6.2 23.4 8.7 yes 30 min prior to cpd 97 10 nmol/kg −41.9 3.0 91.1 25.5 yes 30 min prior to cpd 97 30 nmol/kg −14.7 7.8 150.8 17.3 yes 30 min prior to cpd Vehicle 5 mL/kg 25.8 12.9 14.1 6.9 yes 30 min prior to cpd 63 10 nmol/kg −26.4 5.2 68.2 10.2 yes 30 min prior to cpd 63 30 nmol/kg −23.8 12.1 113.0 40.1 yes 30 min prior to cpd Vehicle 5 mL/kg 30.0 17.4 29.2 14 yes 30 min prior to cpd 126 10 nmol/kg −26.6 6.1 76.1 16.6 yes 30 min prior to cpd 126 30 nmol/kg −46.2 3.9 92.4 30.2 yes 30 min prior to cpd Vehicle 5 mL/kg 2.2 5.2 20.5 7 yes 30 min prior to cpd 399 10 nmol/kg −35.4 3.6 151.0 52.7 yes 30 min prior to cpd 399 30 nmol/kg −45.0 2.9 121.3 15.6 yes 30 min prior to cpd Vehicle 5 mL/kg 11.2 6.5 12.0 8.7 yes 30 min prior to cpd 203 10 nmol/kg −29.5 4.9 54.6 17.3 yes 30 min prior to cpd 203 30 nmol/kg −36.5 5.1 106.9 19.5 yes 30 min prior to cpd Vehicle 5 mL/kg 14.4 7.0 49.9 17.7 yes 30 min prior to cpd 361 10 nmol/kg −23.0 10.6 91.5 14.5 yes 30 min prior to cpd 361 30 nmol/kg −38.1 4.7 93.8 21.1 yes 30 min prior to cpd Vehicle 5 mL/kg 10.7 8.9 31.4 16.6 yes 30 min prior to cpd 7 1.5 nmol/kg 5.4 8.3 80.8 14.3 yes 30 min prior to cpd 7 5 nmol/kg −21.2 9.8 152.9 43.0 yes 30 min prior to cpd Vehicle 5 mL/kg 51.6 16.5 15.5 13.8 yes 30 min prior to cpd 349 10 nmol/kg 4.9 14.3 27.8 13.5 yes 30 min prior to cpd 349 30 nmol/kg −17.3 7.3 100.2 21.8 yes 30 min prior to cpd Vehicle 5 mL/kg 19.9 9.0 39.1 10.6 yes 30 min prior to cpd 224 3 nmol/kg −46.3 4.8 100.3 34 yes 30 min prior to cpd 224 10 nmol/kg −40.0 5.0 132.3 32.6 yes 30 min prior to cpd Vehicle 5 mL/kg 2.5 4.4 10.2 4.9 No 229 10 nmol/kg −36.7 5.2 14.2 9.0 No 229 30 nmol/kg −40.6 2.3 44.5 5.3 No Vehicle 5 mL/kg 7.3 9.2 19.2 4.1 No 289 10 nmol/kg −8.5 7.7 8.9 4.6 No 289 30 nmol/kg −16.1 5.9 7.7 5.6 No

TABLE 17 Glucose Change in GLP-1R KO and WT Mice Treated with GLP-1/Glucagon Peptides GLP-1R WT % KO % KO % glucose glucose glucose change 60 WT change −60 change Somatostatin Peptide Dose min SEM min SEM pretreatment? Vehicle 5 mL/kg −4.1 4.4 16.2 7.4 No 301 10 nmol/kg −43 3.2 29.1 16.1 No 301 30 nmol/kg −35.7 4.3 17.9 7.7 No Vehicle 5 mL/kg 3.7 3.7 6.3 2.1 No 140 10 nmol/kg −32.1 2.8 46.2 6.8 No 140 30 nmol/kg −29.0 3.0 59.8 11.4 No Vehicle 5 mL/kg 9.9 6.9 2.8 3.4 No 188 10 nmol/kg −23.2 3.9 64 15.6 No 188 30 nmol/kg −31.3 2.5 44.6 11.0 No Vehicle 5 mL/kg 10.5 5.4 7.8 4.0 No 195 10 nmol/kg 1.4 3.4 35.3 5.4 No 195 30 nmol/kg −17.0 4.9 48.0 15.1 No

Example 8: Pharmacokinetic Profiling in Pre-Clinical Species

Selected test peptides (n=8) were profiled for pharmacokinetic (PK) properties in the mouse after single intravenous (i.v.) or subcutaneous (s.c.) dose. A subset (n=4) meeting the acceptance criteria was subsequently profiled in the dog (single i.v. dose) and non-human primate (single i.v. and s.c. dose). After administration, blood was sampled up to 48 hrs in the mouse, 120 hrs in the dog and 168 hrs in the non-human primate, at time points selected to accurately determine the full pharmacokinetic profile in each species. Low-binding plasticware containers were used during preparation and sample handling to avoid non-specific binding.

Mouse: PK was studied in lean male C57BL/6 (Peptide 140, Peptide 188, Peptide 195, Peptide 420, Peptide 477 and Peptide 472) or male C57BL/6 DIG pre-conditioned mice on high-fat diet (Peptide 224, Peptide 229). After dosing, PK samples were collected from the dorsal metatarsal vein. Blood of each sample was transferred into plastic micro centrifuge tubes containing EDTA-K2, inverted several times for proper mixing of contents and then placed on wet ice. The blood samples were centrifuged at 4° C. to obtain plasma and stored at −75° C. prior to analysis.

Dog: PK was studied in non-naïve male Beagle dogs. After dosing, PK samples were collected from the jugular vein. Blood of each sample was transferred into plastic micro centrifuge tubes containing EDTA-K2, inverted several times for proper mixing of contents and then placed on wet ice. Plasma was separated by centrifugation and stored frozen in matrix tubes at a temperature set to maintain −20° C. until analysis.

Non-human primate: PK was studied in non-naïve male cynomolgus monkeys. After dosing, PK samples were collected from the femoral vein. Blood of each sample was transferred into plastic micro centrifuge tubes containing EDTA-K2, inverted several times for proper mixing of contents and then placed on wet ice. The blood samples were centrifuged under refrigerated (2° C. to 8° C.) conditions within 30 minutes following sample collection to obtain plasma and stored at −60° C. to −90° C. ° C. prior to analysis.

Formulation: Test articles were formulated in 20 mM Sodium Phosphate, 220 mM Sorbitol pH 7.5 (Peptide 224, Peptide 229, Peptide 140, Peptide 188, Peptide 195) or 20 mM sodium acetate 220 mM mannitol pH 4.5 (Peptide 420, Peptide 477, Peptide 472).

Samples analysis: Samples were analyzed by LC-MS/MS. Calibration standards were injected at the beginning and end of each batch and the determined concentration for each prepared standard was used to construct a calibration curve. Plasma and dose aliquot sample concentrations were determined from the plasma calibration curve.

Data analysis: Plasma concentration data was analyzed by non-compartmental analysis (NCA) using Phoenix Winnonlin v. 8.3.3.33. Linear trapezoidal rule was used for increasing values and log trapezoidal rule was used for decreasing values, applying uniform weighting for lambda_z calculations. Subcutaneous bioavailability was calculated as the ratio AUC(s.c.)_(0-inf)/AUC(i.v.)_(0-inf). Reported values (Table 18) represent the mean of the individual estimates.

Results: Test peptide half-life after intravenous administration and absolute bioavailability after subcutaneous administration calculated by NCA are reported in Table 18. Generally, test peptides displayed pro-longed circulation half-lives in all studied pre-clinical species, and additionally a significant extension in higher order species as compared to rodent. In the mouse, estimated half-lives spanned 2.9-19 hrs, in the dog 86-71 hrs and in non-human primates 49-130 hrs. The bioavailability after subcutaneous administration was generally ≥50%, with comparable levels in the mice and non-human primates. Test peptides evaluated in non-human primates all displayed high bioavailability ≥75%.

TABLE 18 Pre-clinical PK. Half-life after intravenous administration and absolute subcutaneous bioavailability of profiled test peptides in mouse, dog and non-human primate at specified doses. S.c. Half-life i.v. bioavail- Dose administration ability Species Strain Alias nmol/kg h % Mouse C57bl/6 Peptide 10 6.4 102 140 Peptide 10 7.9 98 188 Peptide 10 11 66 195 Peptide 10 5.7 49 420 Peptide 10 2.9 83 472 Peptide 10 8.9 50 477 C57bl/6 Peptide 10 9.5 109 (DIO) 224 Peptide 10 19 86 229 Dog Beagle Peptide 10 75 n.d. 224 Peptide 10 86 n.d. 229 Peptide 10 71 n.d. 188 Peptide 10 78 n.d. 195 NHP Cynomolgus Peptide 10 100 95 224 Peptide 20 130 75 229 Peptide 10 67 79 188 Peptide 10 49 77 195 n.d.: not determined. 

1. A peptide comprising the sequence: H-X2-X3-G-X5-X6-T-S-D-X10-S-X12-αMethyl-Phenylalanine (αMePhe)-L-X15-X16-X17-X18-A-X20-X21-X22-X23-X24-X25-X26-X27-X28-X29-X30-X31-Z, wherein X2 is Aminoisobutyric acid (Aib), S, or A, X3 is Q, H, or E, X5 is T or S, X6 is F or αMePhe, X10 is V, K or Y, X12 is K, E, or S, X15 is D or E, X16 is T, S, or G, X17 is K, R, E, or Q, X18 is R or A, X20 is R, K, or Q, X21 is D or E, X22 is αMePhe or F, X23 is V or, X24 is Q or A, X25 is Aib or W, X26 is L or I, X27 is L, A, E, V, or M, X28 is E, N, A, R, or K, X29 is Aib, T, or G, X30 is G, R, or not present, X31 is G or not present, and Z is amide or acid (SEQ ID NO: 540). 2-39. (canceled)
 40. The peptide of claim 1, wherein X2 is Aib, X12 is K, and X24 is Q.
 41. The peptide of claim 1, wherein X16 is T, X17 is K, X27 is L, X28 is E, and X29 is Aib.
 42. The peptide of claim 1, wherein X3 is Q, X5 is T, X6 is F, X10 is V, X12 is K, X15 is D, X16 is T, X17 is K, X18 is R, X20 is R, X21 is D, X22 is F, X23 is V, X24 is Q, X25 is W, X26 is L, X27 is L, X28 is E, X29 is Aib, X30 is G, X31 is not present, and Z is acid.
 43. The peptide of claim 1, wherein X3 is H, X5 is S, X6 is αMePhe, X10 is V, X12 is K, X15 is D, X16 is S, X17 is R, X18 is A, X20 is K, X21 is D, X22 is αMePhe, X23 is V, X24 is Q, X25 is Aib, X26 is I, X27 is A, X28 is N, X29 is T, X30 is not present, X31 is not present, and Z is amide.
 44. The peptide of claim 1, wherein one or more lysine residues are acylated.
 45. The peptide of claim 44, wherein the lysine at position 17 is acylated.
 46. The peptide of claim 44, wherein the lysine at position 20 is acylated.
 47. The peptide of claim 1, wherein one or more lysine resides are lipidated.
 48. The peptide of claim 47, wherein the lysine at position 17 is lipidated.
 49. The peptide of claim 47, wherein the lysine at position 20 is lipidated.
 50. The peptide of claim 47, wherein the lipid is selected from the group consisting of octadecanedioic acid (C18diacid) and icosanedioic acid (C20diacid).
 51. The peptide of claim 50, wherein the lipid is octadecanedioic acid (C18diacid).
 52. The peptide of claim 50, wherein the lipid is icosanedioic acid (C20diacid).
 53. The peptide of claim 47, wherein the lipid is linked to the epsilon amino group of lysine at position 17 or 20 via a linker.
 54. The peptide of claim 53, wherein the linker is ((O2Oc)-(O2Oc)-γE) or ((O2Oc)-(O2Oc)-γE-γE) in the C- to N-terminal orientation.
 55. The peptide of claim 53, wherein the linker is ((O2Oc)-(O2Oc)-γE) in the C- to N-terminal orientation.
 56. The peptide of claim 54, wherein the linker is ((O2Oc)-(O2Oc)-γE-γE) in the C- to N-terminal orientation.
 57. The peptide of claim 53, wherein the linker is linked to the epsilon amino group of the residue at position 17 or
 20. 58. A peptide comprising the sequence of H-Aib-Q-G-T-F-T-S-D-V-S-K-αMePhe-L-D-T-K-R-A-R-D-F-V-Q-W-L-L-E-Aib-G-acid (SEQ ID NO: 541).
 59. The peptide of claim 58, wherein the lysine at position 17 is acylated and lipidated, the lipid is linked to the acylated lysine via its epsilon amino group to ((O2Oc)-(O2Oc)-γE) linker in the C to N terminal orientation, and the lipid is octadecanedioic acid (C18diacid).
 60. The peptide of claim 58, wherein the lysine at position 17 is acylated and lipidated, the lipid is linked to the acylated lysine via its epsilon amino group to ((O2Oc)-(O2Oc)-γE) linker in the C to N terminal orientation, and wherein the lipid is icosanedioic acid (C20diacid).
 61. A peptide comprising the sequence H-Aib-H-G-S-αMePhe-T-S-D-V-S-K-αMePhe-L-D-S-R-A-A-K(ε-(O2Oc)-(O2Oc)-γE-C18diacid)20-D-αMePhe-V-Q-Aib-I-A-N-T-amide (SEQ ID NO: 228).
 62. A peptide comprising the sequence H-Aib-H-G-S-αMePhe-T-S-D-V-S-K-αMePhe-L-D-S-R-A-A-K(ε-(O2Oc)-(O2Oc)-γE-γE-C20diacid)20-D-αMePhe-V-Q-Aib-I-A-N-T-amide (SEQ ID NO: 233).
 63. The peptide of claim 1, wherein the peptide binds to the GLP-1 receptor (GLP-1R), binds to the glucagon receptor (GCGR), or binds to both a GLP-1 receptor and a glucagon receptor.
 64. The peptide of claim 63, wherein the GLP-1R is a human GLP-1R.
 65. The peptide of claim 63, wherein the GCGR is a human GCGR.
 66. The peptide of claim 1, wherein the peptide is an agonist of GLP-1 activity, an agonist of glucagon activity, or an agonist of both GLP-1 and glucagon activity.
 67. The peptide of claim 1, wherein the peptide has increased proteolytic-resistance relative to the natural ligand of the GLP-1R and/or GCGR.
 68. The peptide of claim 1, wherein the peptide is isolated.
 69. The peptide of claim 1, wherein the peptide has at least 50%, at least 60%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95, or 100% of intact peptide remaining after incubation with a protease at 37° C. for 5 min, 10 min, 15 min, 30 min, 2 hr, 4 hr or 24 hr.
 70. The peptide of claim 69, wherein the protease is selected from the group consisting of neprilysin, pepsin, pancreatin, simulated gastric fluid with pepsin, and simulated intestinal fluid with pancreatin.
 71. The peptide of claim 1, wherein the peptide has a half-life in cynomolgus monkeys after intravenous administration of at least 45 hours, at least 50 hours, at least 60 hours, at least 70 hours, at least 80 hours, at least 90 hours, at least 100 hours, at least 110 hours, at least 120 hours, or about 130 hours.
 72. The peptide of claim 1, wherein the peptide has an s.c. bioavailability in cynomolgus monkeys of at least 75%, at least 80%, at least 90%, or about 95%.
 73. A pharmaceutical composition comprising the peptide of any one of claim
 1. 74. The composition of claim 73, wherein the composition is a solid composition.
 75. The composition of claim 73 wherein the composition is a liquid composition. 